Archive for the ‘Bioinformatics’ Category

Genes and the odds

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Posted 15 May 2012 — by James Street
Category Bioinformatics, Gene sequencing, genetic research, Oncogenes

 

 

genetic mutation

By Amy Jeter
The Virginian-Pilot
©

Iris Byrum told her three grown daughters what she was going to do before she did it.

She broke the news in person, and though she also wanted to tell them what they should do – scream to them not to take any chances with their health – she bit her tongue and remained calm, as usual.

Her own body already had been ravaged twice by an aggressive breast cancer, weakened by the poisons needed to beat it back.

Tissue from her abdomen filled the hole in her chest left by a radical mastectomy. A scar marched across her hips, where surgeons had harvested the flesh and a small crater gaped under her collarbone, where they had carved away a second tumor.

The cancer was 10 years gone but could return at any time.

Byrum didn’t want to go through that again. She didn’t want her daughters to go through that ever – but knew full well that they might. All she could do was try to prepare them.

So Byrum, an operations supervisor with UPS, tracked down Helena and Angie at Angie’s house in Suffolk. She caught up with Mindy at home.

She announced that she was going to find out if cancer ran in the family.

If Byrum tested positive for a gene mutation, her chances of another bout with the disease would rise, and she’d have to ratchet up her defense.

A positive result also meant each of her girls would be faced with a decision: Did they want to know whether they’d inherited the curse?

“At first we were all gung-ho,” said Helena Byrum, the eldest. “Who wouldn’t want to know what their fate is?”

Byrum’s first tumor appeared in 1996 with the suddenness and severity of a gunshot wound.

She was 40 years old and had been in and out of hospitals her whole life. When she was a teenager, doctors implanted a steel rod in her back and encased her in a body cast to correct scoliosis.

Maybe that was why she became the kind of woman who always did the recommended health checks.

In this case, her fastidiousness probably saved her life. Byrum herself found the lump in her breast, less than three weeks after a clean mammogram.

The cancer, already almost the size of a golf ball, was advanced. Her doctors classified it as Stage 3, bordering on Stage 4, the most severe.

Her teenage daughters asked, “Are you going to die?”

Not if she had anything to say about it. A surgeon removed Byrum’s right breast and 19 lymph nodes, to be sure cancer cells hadn’t broken away from the tumor and traveled through her body in her lymph system. Thankfully, her lymph nodes showed no sign of the disease.

Byrum underwent seven months of chemotherapy, but her hair didn’t fall out that time. She kept working, and most people didn’t know she was sick.

In 1997, she found another lump.

This one was a monster, rising ominously under her collarbone. Byrum’s doctors warned about the possible need to remove her collarbone and cut the nerve in her right arm.

Luckily, they didn’t have to go to such extremes. When she awoke from surgery, she could still move her arm. At first, she was horrified, thinking the surgeons hadn’t cut away the tumor, but the nurses quickly assured her that it was a victory.

This time, the treatments pummeled her body for two years. She lost weight, her hair and her fingernails. High-dose chemotherapy made her vomit constantly. She moved to Richmond for six weeks to undergo an experimental stem-cell transplant.

Her husband, Ricky, was working as a longshoreman, and Helena had moved out of the house. Ricky’s brother’s wife, Kim, cared for Byrum. Angie, the middle daughter, cooked her mother’s meals, drove her to chemo treatments and to the emergency room on weekends.

“I maybe saw Mom cry twice,” Angie remembered. “If I was her, I probably would have been crying all the time.”

It took another year for Byrum to begin to feel like herself again.

Even then, she needed to monitor her body closely. Every six months, her blood was tested, her chest was X-rayed and her bones were scanned.

Around that time, Byrum heard about gene mutations that increase cancer risk and wondered if she might have one. In one in 10 patients, cancer is related to a hereditary cause.

The most common mutations causing breast cancer occur in genes called BRCA1 and BRCA2, short for breast cancer susceptibility genes one and two. The genes are supposed to work as tumor suppressors. Inherited mutations in those genes account for an estimated 5 to 10 percent of breast cancers and 10 to 15 percent of ovarian cancers among white women in the United States.

For women who inherit a harmful mutation, the lifetime risk of developing breast cancer is as high as 80 percent, compared with 12 percent for women in the general population. Risk for ovarian cancer is 15 to 40 percent, compared with 1.4 percent. Men with a deleterious mutation on either gene also are at increased risk for breast and possibly other cancers.

Additionally, cancer survivors with a damaged BRCA gene are more likely to develop a new tumor in the breast, ovaries or other site associated with those genes.

Byrum wanted to know if the odds were working against her and her daughters – or even her mother and nieces.

Her family’s cancer history would have provided a clue, but Byrum didn’t know much beyond the fact that her father had died of lung cancer the year before her first diagnosis. Her aunts and uncles were much older than her parents, and no one discussed the specifics of their health.

“It was almost like a secret,” she said.

Intrigued, but cautious, Byrum decided to wait to be tested. She wanted to be sure laws barred insurance companies from hiking premiums or dropping coverage for people with the mutations. She also wanted to be sure the tests were accurate.

In 2008, her doctor said it might be time.

Byrum knew she was opening a can of worms as far as her family was concerned. That’s why she told them all beforehand. If she tested positive, everyone from her sister to her grandsons could carry the gene mutation.

But Byrum was ready for answers. Did her cancer have a source? Was it a fluke? Was it a rogue gene? Could she have passed it on?

She had a feeling about it, and her feelings usually were right. Still, waiting for the result felt a lot like waiting to learn how far her cancer had spread.

The news, when it came, didn’t surprise her. Byrum had a BRCA1 mutation, and she immediately decided to have her left breast and ovaries cut away.

“I was armed with information that was going to prevent me from – hopefully – prevent me from ever having to go through cancer treatment again,” Byrum said. “It was life-saving information, and I was going to use it.”

Two months later, waiting outside the genetic counselor’s office at Virginia Oncology Associates, Helena told her mother about her bargain with God.

If one of the three daughters had to be positive, Helena wanted it to be her.

Angie and Mindy both had children. Helena didn’t. If her sisters were positive, they’d have to worry about whether they’d passed the mutation on to their kids. Helena’s next generation – and its genes – was still a blank slate.

Also, Helena felt she was the most like their mother. She believed she’d inherited her mother’s strength, along with her brown eyes and generous spirit. They even shared a name: Iris Helena Byrum.

They both liked concrete facts.

All three daughters supported their mom’s decision to have the surgeries. They approached the problem differently when it came to themselves.

Helena, who was in her early 30s, figured she would get the test. If the result was positive, she’d go from there.

Angie, two years younger, was caring for a fussy infant. She didn’t want anything else big to worry about: “I thought it would be weird to know.”

Mindy, four years younger than Helena, had more time before the decision became pressing.

Taking the test was easy, Helena found: you just give a little blood. Waiting for the results turned out to be much more difficult.

It was all she could think about: “If I become positive, what do I do? If I become negative, then I don’t have to worry about it. But what if, what if…,”

By the time she finally found herself in the waiting room with her mother, Helena’s anxieties boiled over in tears. Unusual; she normally didn’t cry.

The wait seemed like forever.

Let me be the only one, Helena thought. Let me be the only one.

Byrum said nothing. Though she knew it was absurd, she felt responsible. It weighed on her heart, as a mother.

Let it be negative, Byrum thought. Let it be negative.

Tifany Lewis, the genetic counselor, called them back and asked Helena how she was doing.

“OK,” Helena said. “A little nervous.”

She told Lewis she was all right with whatever happened next.

Lewis told her the result:

Positive.

Helena doesn’t remember much about what happened next.

The tears struck again.

Helena knew the genetic counselor was talking. She tried to concentrate on the words but understood nothing. Lewis’ voice sounded like the muffled-horn noise of adults in Charlie Brown cartoons.

Later, Helena realized that she felt the way people often do when they learn that they have cancer. It was how her mother had felt that second time.

This time, Byrum’s heart was breaking. She wanted to cry, but she knew she needed to be a rock. She reached out her hand to her daughter as Lewis went over charts and described risk.

In later appointments, Helena’s doctors outlined her choices. She could monitor her body through extensive checks every three to four months: mammograms, MRIs, CT scans, ultrasounds, blood tests.

Or she could submit to a double mastectomy and have her ovaries taken out. That would lower her risk for both breast and ovarian cancer to that of the general population.

But concepts like risk and probability proved maddeningly esoteric when Helena tried to apply them to her own flesh and bones.

With each year she lived, she became more likely to develop cancer. That argued for bold action now.

On the other hand, some women with a deleterious mutation never developed cancer. What if she allowed herself to be cut up for no reason?

Like many in her position, Helena first chose the screening option.

For about nine months, she regularly took time off from her job as an office manager for a construction company to sit in waiting rooms and worry about test results. But the stress started to get to her.

Two major obstacles stood in the way of surgeries: Helena still wanted to have a child, so she needed her ovaries. And she wanted to breast-feed.

Only her mother could change her mind about a mastectomy. Byrum told Helena that not being able to breast-feed didn’t mean you were a bad mother. But if Helena developed breast cancer while she was pregnant, that would be a serious problem.

“Do you want to have a baby and raise it?” Byrum asked. “Or do you want to have a baby to breast-feed it?”

The answer was clear, though not easy.

Helena had always been athletic. She didn’t like the thought of mutilating her body, which was what a mastectomy seemed to do, euphemisms aside.

She was so trim that doctors couldn’t even use her own body fat to build new breasts after the surgery. She just didn’t have enough.

In September 2009, Helena had a double mastectomy.

Recovery was tougher than she expected. She rested in her Virginia Beach home for a month and, at first, wasn’t even strong enough to push a fan’s plug into a socket.

Her mind teemed with second thoughts: What did I do? Why did I do this? Did it really happen? Did they really tell me I was positive? Did I make all of this up?

depression weighed her down and stayed until her doctor called one day with news.

They had found precancerous cells in the left breast after it was removed.

“I knew right then that I definitely did the right thing.”

These days, Helena thinks a lot about timelines.

She’s 37, two years beyond her original target age for having a child. Then there’s the ovarian-cancer risk, which continues to increase as she nears 40.

Ovarian cancer is a tricky animal. It’s less common and, in its early stages, less deadly than breast cancer. But it’s also more difficult to find. By the time the disease is detected, it might be too late.

Twice a year, Helena takes time off from her job as an assistant accounting manager to get an ultrasound, and occasionally her doctors will order blood work to check on her ovaries. They don’t pressure her, but they do remind her that precious time is passing, especially after they removed a growth in her uterus last November. It turned out to be nothing.

After Helena got tested, Angie and Mindy did, too.

Angie did it suddenly, almost on a whim, one day in her gynecologist’s office.

She was relieved to learn that she tested negative but felt almost guilty telling Helena about it. Angie thought maybe her role was to be there for her mother and sister.

The more she thought about it, the more she realized that, while it was good news, it didn’t mean she was in the clear. She probably has the same chances as anyone of developing cancer – or any other health problem.

“There’s always something,” said Angie, who is 35.

Mindy, who is 32, tested positive. She is still considering her options.

Helena faces important choices. She has wanted a child ever since she can remember. Her sisters’ boys call her “NeeNee,” and she’s a natural with them, wrestling and playing Nerf darts.

But if Helena has a baby, she could pass along her gene mutation and the agony that goes along with it. Or maybe she wouldn’t.

Helena takes comfort in the thought that scientific advancements could make the whole process less painful decades from now, when her grown child could face a predicament like hers.

She has a little time to make her decision.

Her mother is standing back, ready to step in whenever needed.

“Whatever decision she would make,” Byrum said, “I completely support her, 100 percent.”

 

Amy Jeter, 757-446-2730, amy.jeter@pilotonline.com

 

More than 30 tests are available

Cancer in most patients isn’t associated with an inherited gene mutation.

However, Hampton Roads patients can find out if they carry a gene mutation that increases their cancer risk at Virginia Oncology Associates’ risk reduction clinic.

People with several family members with the same type of cancer or family members who developed the disease when they were younger than 50 might benefit from genetic testing, said Dr. Ranjit Goudar.

At the clinic, a patient first sees Goudar or another oncologist to compile a detailed profile of the patient’s health, family medical history, lifestyle and past. Based on that information, the doctor will determine whether one of more than 30 genetic tests could be appropriate.

If testing is an option, the patient generally will consult with a genetic counselor, such as Tifany Lewis. Together, they’ll discuss the test and how results could affect the patient and family members.

The tests range between a few hundred to several thousand dollars, and most health insurance plans cover most tests.

Whether or not results are positive, Goudar works with patients on ways to stay cancer-free.

“Trying to prevent cancer is the real goal,” Goudar said. “That’s ambitious, but it’s very doable.”

- Amy Jeter

 

DNA Sequencing Lays Foundation for Personalized Cancer Treatment

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Posted 03 Apr 2012 — by James Street
Category Bioinformatics, Gene sequencing, genetic research, Personalized, Washington University Cancer Genome Initiative

ScienceDaily (Apr. 1, 2012) — Scientists at Washington University School of Medicine in St. Louis are using powerful DNA sequencing technology not only to identify mutations at the root of a patient’s tumor — considered key to personalizing cancer treatment — but to map the genetic evolution of disease and monitor response to treatment.

“We’re finding clinically relevant information in the tumor samples we’re sequencing for discovery-oriented research studies,” says Elaine Mardis, PhD, co-director of The Genome Institute at the School of Medicine. “Genome analysis can play a role at multiple time points during a patient’s treatment, to identify ‘driver’ mutations in the tumor genome and to determine whether cells carrying those mutations have been eliminated by treatment.”

This work is helping to guide the design of future cancer clinical trials in which treatment decisions are based on results of sequencing, says Mardis, who is speaking April 1 at the opening plenary session of the American Association for Cancer Research annual meeting in Chicago. She also is affiliated with the Siteman Cancer Center at the School of Medicine and Barnes-Jewish Hospital.

To date, Mardis and her colleagues have sequenced all the DNA — the genome — of tumor cells from more than 700 cancer patients. By comparing the genetic sequences in the tumor cells to healthy cells from the same patient, they can identify mutations underlying each patient’s cancer.

Already, information gleaned through whole-genome sequencing is pushing researchers to reclassify tumors based on their genetic makeup rather than their location in the body. In patients with breast cancer, for example, Mardis and her colleagues have found numerous driver mutations in genes that have not previously been associated with breast tumors.

A number of these genes have been identified in prostate, colorectal, lung or skin cancer, as well as leukemia and other cancers. Drugs that target mutations in these genes, including imatinib, ruxolitinib and sunitinib, while not approved for breast cancer, are already on the market for other cancers.

“We are finding genetic mutations in multiple tumor types that could potentially be targeted with drugs that are already available,” Mardis says.

She predicts, however, that it may require a paradigm change for oncologists to evaluate the potential benefits of individualized cancer therapy. While clinical trials typically involve randomly assigning patients to a particular treatment regimen, a personalized medicine approach calls for choosing drugs based on the underlying mutations in each patient’s tumor.

“Having all treatment options available for every patient doesn’t fit neatly into the confines of a carefully designed clinical trial,” Mardis acknowledges. “We’re going to need more flexibility.”

When during the course of cancer mutations develop also is likely to be important in decisions about treatment. In a recent study, Mardis and her team mapped the genetic evolution of leukemia and found clues to suggest that targeted cancer drugs should be aimed at mutations that develop early in the course of the disease.

Using “deep digital sequencing,” a technique developed at The Genome Institute, they sequenced individual mutations in patients’ tumor samples more than 1,000 times each. This provides a read-out of the frequency of each mutation in a patient’s tumor genome and allowed the researchers to map the genetic evolution of cancer cells as the disease progressed.

They found that as cancer evolves, tumors acquire new mutations but always retain the original cluster of mutations that made the cells cancerous in the first place. Their discovery suggests that drugs targeted to cancer may be more effective if they are directed toward genetic changes that occur early in the course of cancer. Drugs that target mutations found exclusively in later-evolving cancer cells likely may not have much effect on the disease because they would not kill all the tumor cells.

Mardis says that sequencing the entire genome of cancer cells is essential to piecing together an accurate picture of the way cancer cells evolve. If the researchers had sequenced only the small portion of the genome that involves genes, they would not have had the statistical power to track the frequency of mutations over time. (Only 1 to 2 percent of the genome consists of genes.)

In another study, a phase III clinical trial of post-menopausal women with estrogen-receptor positive breast cancer, the Washington University researchers have shown that sequencing can help to predict which women will respond to treatment with aromatase inhibitors. These estrogen-lowering drugs are often prescribed to shrink breast tumors before surgery. But only about half of women with estrogen-receptor positive breast cancer respond to these drugs, and doctors have not been able to predict which patients will benefit.

Interestingly, by sequencing patients’ breast tumors before and after aromatase inhibitor therapy, the researchers identified substantive genomic changes that had occurred in responsive patients, whereas the genomes of unresponsive patients remained largely unchanged by the therapy.

“No one has ever looked at treatment response at this level of resolution,” Mardis says. “It’s so obvious who is responding.”

In addition, the researchers have identified a series of mutations in the breast tumors that have corresponding small-molecule inhibitor drugs that target defective proteins. This finding indicates that for women who are not responding to aromatase inhibitors, treatment options may include combining conventional chemotherapy with the indicated small-molecule inhibitor.

“We felt it was important to show there could be therapeutic options available to patients who are resistant to aromatase inhibitors,” Mardis says. “As we move forward, we think sequencing will contribute crucial information to determining the best treatment options for patients.”

The research is funded by the National Cancer Institute, the National Human Genome Research Institute and the National Heart, Lung and Blood Institute, all of the National Institutes of Health, and the Washington University Cancer Genome Initiative.

The coming medical revolution

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Posted 26 Mar 2012 — by James Street
Category Bioinformatics, Books
Sunday, Feb 19, 2012 3:00 PM Pacific Daylight Time

Technology has the potential to transform our concept of sickness. An expert explains what the future holds

By Lucy McKeon

Interview with Author of the creative destruction of medicine about technology and medicine

The information at our everyday disposal is growing at a breathtaking rate. From the beginning of civilization to 2003, the world accumulated 1 billion gigabytes of data. Today, we create 1 trillion gigabytes every year. These advances have transformed the way we think about knowledge, communication and countless aspects of our everyday life — and they have the potential to revolutionize the way we think about our own health.

In his new book, “The Creative Destruction of Medicine: How the Digital Revolution Will Create Better Health Care,” Eric Topol, a former professor and researcher at the University of Michigan and Case Western University, and chief academic officer for Scripps Health, a nonprofit healthcare system based in San Diego, argues that the digital revolution can democratize our medical system. Topol demonstrates how the digital revolution can be used to change individual care and  prevention, and even the economics of American healthcare. From cellphones that automatically collect medical data, to biosensors, advanced imaging, individualized prescriptions and gene-specific drugs, Topol’s book leads readers through science-fiction-sounding scenarios that may soon be a reality.

Salon spoke with Topol over the phone about the empowered consumer, rebooting the life science industry, and the doctors of the future. 

“Digitizing the human” is a provocative phrase you use throughout the book; what does this mean, and how can it lead to what you call the “democratization of medicine”?

We’re so used to digitizing everything — books and movies and periodicals — everything except for our bodies. My idea is to digitize the essence of what makes us tick — our genome and our physiology — thanks to different biosensors which are largely wearable, put right on a band-aid or a wrist or on the sole of a shoe. This would be combined with imaging, the ability to image any part of the body with a high-resolution pocket ultrasound device. When you take all these things together, along with personalized electronic health records and health information systems, this gives us a really panoramic, deep view of each individual.

How do cellphones fit into this?

Well, the cellphone has been the basis of a lot of democratization. You look at the Arab Spring and the Occupy movement and it’s the mobile phones that are bringing people together, through Facebook and Twitter and sharing pictures and videos and emotions. Now the digital infrastructure supports the whole medical side of this; you could have your own data for blood pressure or glucose or mood or anything quantified, right on your phone. And then that information can be shared with your social network, or your doctor, or whoever.

So the ability to have this mini computer in your pocket, that you’re essentially surgically attached to, is such a powerful force for the use of that data.

What role will the consumers play in this revolutionary shift?

I envision the consumer being the primary driver. That’s why I actually wrote the book. I’ve written a lot of medical textbooks, and I’ve lived in the medical microcosm until recent years, but then I started realizing that this digital world is really changing everything. The medical community itself is so resistant to change. The government and the life science industry are not going to be active in promoting a radical change. But consumers can do it and they’re more truly empowered, more resourceful and bound together and powerful than ever before.

And there’s one other lesson that’s really valuable: Back in 1997, the United States approved Direct to Consumer Advertising on TV for drugs, which I think was a dreadful mistake, by the way. But what’s interesting about it was it basically fueled this “Ask your Doctor” movement: a patient-centered, consumer-centered model. It was very powerful because of course these drugs [being advertised] became extraordinarily widely used. I don’t want to promote that, but on the other hand, if consumers are partnering with doctors, like, “Here’s my genome, Doctor, what do you think of it? Here’s my blood pressure and vital signs for the last three months,” it’s not just “ask your doctor” anymore it’s tell your doctor, share with your doctor.

Why is the medical field so resistant to digitization/digital records? Other industries have done this almost a decade ago.

Well, this is the history of medicine. If you go back to 1816 when the stethoscope was invented, it took 20 years before doctors would use them. The average time it takes for a medical innovation to come into daily practice is 17 years, which is just horrible. And they had all kinds of excuses, similar to the excuses that they have today. Basically, one of the main reasons doctors wouldn’t use a stethoscope was because they said it would interfere with their interactions with patients. And they didn’t want to learn all these new heart sounds and breath sounds and that sort of thing.

There’s an unwillingness to change. For example, a lot of physicians I work with are bothered by the fact that they have to be typing at a computer, looking at a screen, rather than interacting with a patient. And I understand that; both the physician and the patient take a hit in terms of optimal communication. How do we deal with that? A lot of physicians now have scribes that do the computing of data while they never lose eye contact with the patient. The patient obviously knows very well whether they’re not being listened to or looked at. So part of it is resistance to change and part of it is losing touch with a visit with a patient.

You mention this in your book, but isn’t it dangerous to have our medical files out there, in terms of security issues?

Like everything else that’s digitized, when you digitize a human being you have the potential for hacking, privacy and security issues. And already there have been breaches of electronic medical records in major medical centers around the country. So this has to be attended to with the maximal assurance that we’ll do everything we can to preserve that security. It’s a tradeoff: Do the benefits of having the essence of each individual captured digitally override the hopefully small, negligible risk of a breach of that data?

How do American doctors compare to doctors in other countries in terms of their attitudes toward technology?

Medicine on a planetary basis, on a global basis, is very conservative and resistant to change. But there are some specific examples where there’s a real gradient or heterogeneity, a real marked difference in cultures. In the U.S. the adoption of technology can be stymied because of reimbursement issues. In other countries where there’s no fee-for-service private practice, there’s been remarkable adoption of certain technologies. A great example of that is the portable ultrasound; I haven’t used a stethoscope now in two years. I use this pocket ultrasound device so I can see everything in the heart rather than listen to the heart’s sound. In the U.S., hardly any doctors are using that because they can’t get reimbursed; they much prefer to send the patient to get a cardiogram, which is an ultrasound of the heart, or an ultrasound of the abdomen or whatever the ultrasound is. Whereas in India, Brazil, China, this is one of the hottest new technologies because it saves costs dramatically and there are no issues with respect to reimbursement.

In what ways can recent breakthroughs in our understanding of the genome – from the Human Genome Project of 2000 to today – contribute to the shift to individual-based medicine?

There are three biggies right now. The longest chapter in the whole book is on genomics. The first is pharmacogenomics. Now, in the U.S. alone, we spend $350 billion a year for prescription medicines, and so many of these drugs have known serious side effects, that can be predicted by knowing a particular genotype. And in addition, some medicines don’t work for a lot of people, and we could predict that with a very simple genotype — like Plavix, which a third of people don’t respond to but they keep taking every day, or Metformin for diabetes, which 25 percent of patients don’t respond to. Tegretol has a horrendous side-effect profile. We don’t screen for it in the U.S., but you can’t get a Tegretol prescription in Taiwan without having a genotype. So in that sense we’re way behind. I could go on, a lot more examples are in the book, but that’s No. 1 – the use of genomics today. We’re not leveraging that great new knowledge.

Second is in the field of cancer therapeutics. If you have a new diagnosis of a significant cancer today, the best way to potentially get the right therapy is to get a whole genome sequence of the tumor, and also of your native so-called germline DNA, and compare the two. By comparing the mutation in the tumor to what you’re born with in your DNA, you can see what went off the tracks (because cancer is by definition a genomic disease) and then you can fashion a therapy specifically for that individual.

The third area is the elimination of the idiopathic, which is a very fancy medical term used for “we don’t know.” There’s a lot of people walking around with debilitating serious disease, and trying to get a diagnosis for what is wrong with them and they haven’t been able to do it. The issue is, until now we didn’t have a way to sort this thing out but with whole genome sequencing, we can in many of these individuals determine the root cause, the biologic basis for their illness.

Competing manufacturers of these new technologies will be required to agree upon uniform standards; is this a feasible hope?

This is a really interesting trend to watch. Now in the networking electronic world we live in, you see some unprecedented collaboration among even competing life science industry companies. So, for example, in the case of Alzheimer’s disease, where they haven’t come up with anything to prevent or change the course of Alzheimer’s, it’s been very frustrating. Many companies have invested billions of dollars in this whole objective. But now, they are working together. So most of the large pharma companies are pooling their data to basically do an autopsy of the failed drugs to find out what went wrong. And you never would have seen that in the past – I mean that’s actually remarkable.

If everyone working on cancer that did a genome sequence of an affected individual put that data in a common place and all the companies were also involved, we could really get so far ahead in this cancer problem, which is quickly emerging as the No. 1 cause of death, overriding heart disease. But we don’t have that type of collaboration yet. We need it to cross national boundaries, and to get the academic and life science industries to converge. That would be creative destruction in high gear!

What technological innovations in medicine are you most excited about? 

I think the one I’m most excited about is the embedded nano-sensor. You have to put it in the bloodstream and get it to localize, either in the finger or the wrist, someplace that’s hyper handy that will communicate with your cellphone. And that embedded nano-sensor can be used to pick up, for example, the first cancer cell that shows up in the bloodstream, which would promote the earliest possible detection of cancer.

It also could help with the autoimmune form of diabetes, called Type 1, which usually affects kids. If we have that embedded nano-sensor constantly monitoring, and a medicine used to block the immune system when needed, this, hopefully, could lead to the end of autoimmune diabetes, which is really exciting.

And the other really far out thing is the area of heart attack prevention, again through an embedded nano-sensor. It can be used to pick up cells in an artery that’s starting to crack a week or two before a heart attack. We have some really good data to suggest that this will ultimately be possible.

How does Obamacare fit into this? How much will this cost? Where will the money come from?

Obamacare is in a different orbit. There’s nothing in the 2,000-plus page bill that gets into this kind of hyper innovative individual medicine, biosensor leveraging, genome and all these sorts of things – it doesn’t really show up. But it is a great opportunity to make medicine and healthcare more affordable. For example, it’s estimated that about a third of the $350 billion spent a year on prescriptions is a total waste. So there’s a great opportunity there, with gene-specific drugs. If we do the 20 million echocardiograms, and almost as many abdominal and fetal ultrasounds, for free with ultrasound pocket devices, there are billions of dollar we could save there. With sensors, if we could get tens of millions of people in this country to manage or prevent their diabetes that could have enormous financial implications. And it’s the same for high blood pressure: 50 percent of people with high blood pressure do not have it adequately managed, so they’re vulnerable for strokes and heart attacks. If we can manage it with a simple cellphone sensor, that would be an enormous potential to lower costs for stroke disabilities, heart attack, heart failure, all those sorts of things.

In what ways can social networking be useful for physicians?

Patients share on online health communities and each of these social networks have amassed an enormous following. Let’s say you have a particular condition like multiple sclerosis, or a form of cancer or diabetes. You go on these social networks and find peers whom you’ve never met with, but they become your guidance and connections. And they are now more trusted than doctors by a substantial proportion of participants in these online health communities. Now, on the doctor side, almost 90 percent don’t even know these online communities exist, which is in itself surprising. But, if we work together, this is another opportunity to get information out there.

On the other hand, you don’t exactly want to have your patient as your Facebook friend. But one thing that’s striking me is, just a couple weeks ago in the Wall Street Journal there was this big debate: Should doctors email with their patients? And I thought, “How could that even be a question?” It seemed like a crazy throwback to a different era. Then there was an article in the Journal of American Medical Association asking, should patients be able to access their laboratory data? You’ve gotta be kidding. How could this be a question in 2012? This is the paternalistic, Doctor Knows Best mind-set that is still carrying over to today. We’re too far away from democratization, and I’m hoping we can change that.

What does all this mean for the individual consumer? How will our actual experience of going to the doctor of the future change?

The doctor of the future, who has plasticity and has moved into the digital era, will be up on all these things. There may not be in-office visits, there may be virtual visits on Skype or Facetime, and patients could send all their data real time through their phone. I think each physician has to say [to patients], We want you to have all your data. We want you to be participatory. We need you to be fully engaged. And if you’re fully engaged, you’re the one with the most vested interest in your condition. We want you to have all the data, whether it’s your lab test, your notes, your metrics on your phone, your genomic data, your scans, whatever it is, we want you to have it because we want you to help drive this process.

Lucy McKeon is an editorial fellow at Salon. More Lucy McKeon

Why Doctors Need to Embrace Their Digital Future Now

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Posted 26 Mar 2012 — by James Street
Category Bioinformatics, Books
Photo: Gregg SegalWe understand digitizing a book, but what does it mean to digitize a human being? asks Eric Topol.
Photo: Gregg Segal

Medicine has certainly progressed in the past 50 years, but the day when tricorders diagnose every ailment instantly and treatments are tailored to our DNA seems as far off as ever. Eric Topol is trying to bridge that gap. In his new book, The Creative Destruction of Medicine, Topol—the chief academic officer at Scripps Health—calls on patients to demand true digital medicine now. We talked to him about genetics, gadgets, and his vision of a Khan Academy for doctors.

Wired: Not many doctors get to take the stage at the Consumer Electronics Show, as you did in 2010. What was that like?

Eric Topol: It was a revelation. Normally people go to CES to learn about gizmos like HDTVs. And here I come to do a demo of wireless devices for health. The reaction was astounding: They began clapping when this little device I was holding showed an ultrasound of my heart on the big screen. It made me realize that consumers want to care about their health. They just need to get activated.

Wired: And that starts with this nifty concept you have of digitizing medicine.

Topol: Right. We understand digitizing a book, but what does it mean to digitize a human being? When I went to medical school, the term digital applied only to rectal exams. But today you can get a DNA sequence, you can get biosensors that record nearly every physiologic metric from blood pressure to brain waves, you can get a digital scan of any part of the body. These tools offer a window into each person that was unfathomable a few years ago.

Wired: But it’s not just the body; this scales up to the entire infrastructure of medicine.

Topol: That’s right. The digital world—the Internet and the cloud and supercomputing and social networking—is breaking medicine out of its cocoon. It’s a superconvergence we’ve seen in other walks of life but not in the health and medical sphere.

Wired: So what does digitized medicine get us?

Topol: We can start capturing people’s health data throughout their lives—all the little things that have lasting implications. For instance, we can track cumulative radiation exposure from every scan and x-ray. And consider the risk of drug interactions: Every year hundreds of thousands of Americans wind up in hospitals or worse because we didn’t match up the patient genomically with the right drug or dosage. Just capturing those things could save thousands of lives.

Wired: How do we make this happen now, rather than just waiting for a new, net-savvy generation of doctors?

Topol: We need a Khan Academy for doctors: captivating 15-minute videos on genomics, on wireless sensors, on advanced imaging, on health information systems. These things can revive the excitement they felt as premeds, when they first decided to go into this field. If we can get practicing physicians up to speed and really inspired, maybe we won’t have to wait a generation. I shudder to think about waiting 10 or 20 years for this transformation to occur.

Wired: But there are obstacles. For instance, many people in the tech world are afraid of running into bottlenecks getting FDA approval for new medical devices.

 

Topol: The FDA is moving very slowly, with considerable restraint and resistance. That’s one reason the technology is years behind where it should be. One example is a device called AliveCor. It’s a couple of sensors on a case that you can put on the back of an iPhone or a Droid phone to get your electrocardiogram and heart rhythm. It’s very inexpensive—less than $100. You can even send the results to your Facebook friends. In Europe it’s already approved and available today. But not in the US. A lot of these great, innovative ideas like sensors or rapid point-of-care geno-typing are moving slowly through the process with a considerable lack of support, as I see it. And these are largely just diagnostic tools, not therapeutics.

Wired: Meaning that they’re not doing anything to your body; they’re just taking information.

Topol: Exactly. A perfect example would be the glucose sensor that you can put on and get a reading every five minutes.

 

Wired: Which has likewise been hung up in FDA limbo.

Topol: Yeah. If you’re a diabetic and you’re using a glucose sensor, you have to carry your phone and another device, because the FDA doesn’t want glucose going through the phone. That’s really unfortunate; people would rather not pull out a glucose monitor in public. If it were in their phone, it would look like they’re just checking email.

Wired: But people with diabetes have many tools to manage their disease, and they’re self-tracking their care. You could argue that’s the epitome of digitizing medicine and giving people access to tools. They should feel empowered. But here’s what I call the diabetic’s paradox: When you survey them about these tools, they say they’re a source of frustration and anxiety—all these negative emotions. Giving them this responsibility and the tools seems to be a burden.

Topol: That’s an important issue. Will having more information induce fear and anxiety? I personally believe that if the information is easy to obtain and work with, most people would want to have it. For diabetes in particular, we know there’s a relationship between lack of glucose regulation and complications like blindness and kidney failure. So if you were diabetic and you knew that you could get your glucose in a tight, normal range just by adjusting your lifestyle, wouldn’t that be great? It could be rather seamless in your life. And you could look at your data and start to figure out what works in you: How much do exercise and certain foods help? What’s going on in your life that gets your glucose out of whack? But instead, what we have now requires finger sticks multiple times per day, the ranges are fuzzy and inexact, and the tools are horrible. As long as it doesn’t involve pain, as long as it’s simple to use out of the box, this will work. This will be better. That’s what we’re aiming for.

Wired: You write a lot about imaging—x-rays, CT scans, MRIs—and how that’s all gone digital. And that’s very much a two-edged sword, as you well know.

Topol: Absolutely. We are grossly overusing imaging in this country, and that’s really scary to me. The mass use of radiation scans is way out of line with any other place in the world. There are estimates that 2 to 3 percent of cancers in the US each year are engendered by exposure to repetitive imaging. So I present this as a shout-out to consumers. When you’re asked to have a CT scan or a nuclear scan, do you know how much radiation that involves? How many of those sorts of scans have you already had? Is it necessary? Is there an alternative? I don’t think many people know about that. We need tools that let us track our radiation exposure for ourselves, each of us. So that, I think, is an important part of how we can reboot the future of medicine.

Single-cell sequencing leads to a new era of cancer research

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Posted 05 Mar 2012 — by James Street
Category Bioinformatics, Gene sequencing, genetic research

March 2, 2012 in Genetics

BGI, the world’s largest genomics organization, developed single-cell genome sequencing technology and published two research papers for cancer single-cell sequencing in the research journal Cell. In the papers, which were published today in the same issue of Cell, BGI researchers applied their new single-cell sequencing (SCS) method to identify the genetic characteristics of essential thrombocythemia (ET, a kind of blood neoplasm) and clear cell renal cell carcinoma (ccRCC, a typical kidney cancer), and demonstrated that single cell analyses of highly heterogeneous tissues provide much clearer intratumoral genetic pictures and developmental history than previous bulk tissue sequencing.

The availability of BGI’s SCS method opens new ways for the genetic study of tumors at single nucleotide resolution, especially for those where it is difficult to identify key mutations by previous bulk tissue sequencing. The single-nucleotide resolution of this method enables application to a variety of diseases and biological processes, such as studies on cellular heterogeneity of tissues, iPS or , pre-implantation and the of .

Cells are heterogeneous in . The current high-throughput sequencing technology has been applied in a variety of fields of biological study, however, its obvious limitations on studying complex phenomena such as tumor evolution, , neuron science, and Meta genomics make it powerless on heterogeneous samples. Recently emerging single-cell analysis approaches like single-nuclei sequencing on breast cancers by Navin et al. throw light on understanding the biology underlying cellular heterogeneity.

Until now, there has been no suitable way for scientists to explore the genetics of single at a single-nucleotide resolution. To overcome this deficiency, researchers from BGI developed a high-throughput single-cell sequencing method based on an advanced multiple displacement amplification (MDA), and tested it using two single lymphoblastoid cells derived from a healthy individual (YH) who provided DNA for the first Asian diploid genome sequence. “Through the evaluation, we found our MDA-based method could provide greater resolution and genome coverage, which will enable single-cell analyses at a single-nucleotide level with relatively high sensitivity and specificity,” said Luting Song, the leading author of this study and project manager at BGI.

BGI first applied its new SCS method to conduct single-cell exome analysis of the blood neoplasm because it is much more convenient to infer the development process underlying the abnormal proliferation of hematopoietic progenitor cells. Results revealed the JAK2-negative blood neoplasm may arise from monoclonal somatic mutant cells, and identified several known and novel mutated genes that may play roles in the blood neoplasm initiation and progression. Therefore, the identified mutated genes may be of interest for future biological research.

In addition, to better understand the intratumoral genetics underlying mutations of typical solid tumor, BGI researchers applied this new method to kidney tumor. The study demonstrates it is unlikely that this tumor resulted from two most common mutations in VHL and PBRM1. This emphasizes the importance of assessing and diagnosing cancers and patients at an individual level to determine the most effective treatment. Further analysis indicated that this tumor did not contain any significant clonal subpopulation. Quantification analysis of tumor heterogeneity showed that most of the somatic mutations occurred only in a small fraction of the cells, and that mutations with different allele frequencies showed very different mutation spectrums. Researchers also screened for mutations in a group of 98 kidney tumor patients and identified potential key genes contributing to the establishment of this kidney tumor.

“Our pilot study demonstrates kidney tumor may be more genetically complex than previously thought and provides novel information that can lead to new ways to investigate individual tumors with the aim of developing more effective cellular targeted therapies,” said Xun Xu, Vice Director of BGI. “This study also provides a good example of how single-cell exome sequencing could yield novel biological insights for an individual solid tumor.”

“Our two studies demonstrate the power of our proprietary method for identifying complex, small genetic changes in a heterogeneous tumor at a greater resolution,” said Yingrui Li, Vice Director of BGI. “I believe our study will enable researchers to develop new methods to clinically evaluate tumors and promote the research of complex diseases and biological processes.”

Jun Wang, Executive Director of BGI, said, “BGI’s single-cell sequencing technology elevates genomic studies to a new level, enabling researchers to conduct biological studies at the cellular level in life processes such as the growth, reproduction and development, heredity and aberrance of organisms.”

Provided by BGI Shenzhen

SA 1000 Cancer Genome Project banking tumors of patients

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Posted 25 Feb 2012 — by James Street
Category Bioinformatics, Gene sequencing, genetic research

by Wendy Rigby / KENS 5

Bio | Email

Posted on February 24, 2012 at 2:54 PM

SAN ANTONIO — A San Antonio cancer doctor is launching an ambitious new project. It’s a unique tumor bank that will help unravel the genetic puzzle of a killer disease.

Lori Vanta of San Antonio has been fighting colorectal cancer since 2008. At age 41, she’s already undergone treatment with surgery, radiation and chemotherapy.
“I have a lot of living to do,” Vanta said. “I have two beautiful children and I’m not ready to give up. I’ll never stop fighting and I’ll never stop hoping and helping.”
Vanta is helping by donating her tumor and blood to the San Antonio 1000 Cancer Genome Project which is gathering samples of the ten most common cancers in San Antonio.
It’s the brainchild of Dr. Anthony Tolcher. He has enlisted the help of more than a hundred other San Antonio doctors as well as Rackspace to gather, process and upload data about thousands of tumors.
“It is a community effort to try to understand, fully understand, the genetic abnormalities that lead to cancer and what happens to those patients with those genetic abnormalities,” Tolcher, an oncologist, explained.
That information yields a diagram showing the mutations of chromosomes in individual patients. Analysis will help doctors target therapies and come up with better treatments. Scientists from all over the world will have access to the information.
In three years, the group hopes to have a thousand tumors mapped this way.
“Once you explain what it’s going to do and what’s involved, I think people really want to participate because most patients want to see the scientific field move forward,” Tolcher commented.
“It’s all working toward helping us specifically, for my tumors and for my cancer to specifically help me,” Vanta stated. “And it’s amazing. It’s mind-boggling.”
It will take several million dollars to map the whole genome sequences of these tumors. Tolcher is raising money through a non-profit group. In just six weeks, the San Antonio 1000 Cancer Genome Project has already raised almost $250,000.

An ambitious plan for curing cancer in a businesslike way is in the works

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Posted 28 Dec 2011 — by James Street
Category Bioinformatics, Finance and Politics of cancer research and treatment, General Cancer Research, genetic research, Proteomics, Proteomics, Research Centers, Understanding Cancer

Dec 31st 2011 | NEW YORK | from the print edition

 

Cancer, you have a problem

RON DEPINHO is a man on a mission. Oddly, though, he does not yet know exactly what that mission is. Dr DePinho is the new president of the MD Anderson Cancer Centre in Houston, Texas. (He took over in September, having previously headed the Belfer Institute, part of Harvard’s Dana-Farber Cancer Institute.) Mindful of his adopted city’s most famous scientific role, as home to Mission Control for the Apollo project, he says his own mission is akin to a moon shot. He aims to cure not one but five varieties of cancer. What he has not yet decided is: which five?

That it is possible to talk of curing even one sort of cancer is largely thanks to an outfit called the International Cancer Genome Consortium. Researchers belonging to this group, which involves 39 projects in four continents, are using high-throughput DNA-sequencing to examine 50 sorts of tumour. They are comparing the mutations in many examples of each type, to find which are common to a type (and thus, presumably, causative) and which are mere accidents. (The DNA-repair apparatus in malignant cells often goes wrong, so such accidents are common.)

The consortium’s work is progressing fast, and preliminary results for many tumours are already in. But such knowledge is useless unless it can be translated into treatment. That is where Dr DePinho comes in—for his career has taken him into the boardroom as well as the clinic. He is a serial entrepreneur: he helped found Aveo Pharmaceuticals, which is developing a drug to block the growth of blood vessels in tumours, Metamark Genetics, which works on diagnosing cancers, and Karyopharm Therapeutics, which is trying to regulate the passage of molecules into and out of the cell nucleus, and thus control the nucleus’s activities. His aim in coming to MD Anderson, he says, is to “industrialise” other aspects of biological research in the way that genetics has been pushed forward by high-throughput sequencing.

That will cost billions of dollars. Fortunately, the state of Texas—no pushover when it comes to spending taxpayers’ cash—is creating a $3 billion cancer-research fund to help pay for it. Local philanthropists, including T. Boone Pickens and Ross Perot, are chipping in, too. Their model is the original Human Genome Project, during which the cost of sequencing a single genetic “letter” (a DNA base pair) fell from $10 in 1991 to ten cents in 2001—and is now 3,000 base pairs a cent. They hope their dollars will encourage people working with what are now, essentially, craft technologies to think about how they might industrialise them.

Several techniques look ripe for such industrialisation. Dr DePinho sets great store, for example, by the use of genetically modified mice (he calls them “little patients”) in which mutations found in human cancers can be replicated precisely, but one at a time, to discover the shape of each piece of the jigsaw. If this process can be scaled up it will, as he puts it, allow cancer’s genetic generals to be distinguished from the foot soldiers.

Another field that has great potential is imaging technology—in particular, a combination of positron-emission tomography (which uses radioactive sugar to measure how metabolically active tissue is) and computerised tomography (which uses X-rays to map the body’s internal anatomy). Together these can show whether a treatment is reducing a cancer’s energy consumption, and thus its metabolism. This gives a good indication of how well that treatment is working.

A family business

Dr DePinho himself will have more duties at MD Anderson than just dealing with the five chosen tumours. The donkey work of creating the Institute for Applied Cancer Science, as the new mission control is to be known, will be done by Lynda Chin. Dr Chin, too, worked at the Belfer Institute. She is part of the International Scientific Steering Committee of the cancer-genome project. And she is also Dr DePinho’s wife. Dr Chin will be assisted by some 55 other scientists from the Belfer, who are making the journey to Texas with her and her husband. That sort of team poaching is common in investment banking but rarer in academic research. Dr DePinho refers to it, jokingly, as metastasis, since a clone of his primary creation will be taking root elsewhere in the country.

As to which five cancers to attack, that decision will be made by the middle of 2012. A crucial consideration will be how likely it looks that research into the tumour in question could get rapidly to the “proof of concept” stage—the point at which it could be taken forward by a business that relied on commercial sources of capital, rather than on the sorts of grants that usually propel academic research. At that moment a new firm might be spun out of the institute, or a deal might be done with an established pharmaceutical firm, to try to get a new drug developed.

In recent years many big drug companies have gutted their research departments. This is partly because those departments have failed to come up with new “blockbuster” drugs of the sort that created Big Pharma in the first place, and partly because the big firms’ bosses had hoped that smaller biotechnology companies, of the sort Dr DePinho has helped set up, would do the hard work of drug discovery instead, and then let themselves be bought by the big firms.

Unfortunately, it hasn’t quite worked out like that. The output of the biotech firms has been a trickle, rather than a torrent. They have been one of the worst-performing parts of the private-equity market since 2007, according to Dr DePinho. He hopes to change that—and in the matter of new anti-cancer drugs, the science is looking auspicious. For example, a drug called vemurafenib, which was approved for use in America in August 2011, gives months of extra life to people with metastasising melanoma, one of the deadliest cancers. Vemurafenib is so powerful that some people call it a “Lazarus” drug, after the chap Jesus is said to have raised from the dead.

Crucially for Dr DePinho’s project, the development of vemurafenib was stimulated by the identification of a mutated gene often present in melanomas. He and others like him hope that the cancer-genome consortium will throw up dozens of similar genes, and that they, too, will prove tractable targets for drug development.

Of course, if Dr DePinho had a penny for every time a “cure for cancer” headline proved premature, he wouldn’t need munificent donors. But if his bets on the science and on adopting business methods pay off, the drug industry and millions of patients will benefit. That would be one benign sort of metastasis.

With Death, Christopher Hitchens And Steve Jobs Showed Us The Limits Of DNA Sequencing

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Posted 17 Dec 2011 — by James Street
Category Bioinformatics, Gene sequencing, genetic research

Matthew Herper

Matthew Herper, Forbes Staff

Christopher Hitchens, quite famously, did not believe in miracles. His death is a reminder that we shouldn’t, either – even when they’re the scientific kind.

Hitchens, like Steve Jobs, was among the first patients to benefit from a very new technology: the use of DNA sequencing to pick cancer drugs that might have a better chance of slowing a tumor’s growth.

Cells become cancerous because of mutations in their DNA that make them stop behaving as discrete parts of the body and instead cause them to multiply like crazy and run amok. Once a cell is cancer, its genes get twisted and re-arranged even more. The idea is that by identifying some of these mutations, doctors can figure out which drugs are most likely to stop or slow tumor growth and prolong life.

Jobs was so excited by this idea that he told his biographer, Walter Isaacson, that he could be among the first to outrun cancer this way or be among the last to die from it. Both DNA from Jobs’ tumor and Jobs’ own cells was sequenced — the most expensive and exhaustive way to look for tumor-causing defects. (A cheaper way is to just look at genes known to correlate with effectiveness for existing drugs in some cancers.)

Characteristically, Hitchens did not get nearly as excited as Jobs did about the prospect, but he still seemed filled with hope. “At least it spares me some of the boredom of being a cancer patient because what I’m going through is very absorbing and positively inspiring,” he told the Daily Telegraph. “But if it doesn’t work, I don’t know what they could try next.”

Also characteristically, the story of sequencing Hitchens’ tumor is full of larger-than-life debates about belief and nonbelief, God and the absence thereof. He was approached by Francis Collins, a devout Christian and head of the National Institutes of Health. A decade ago, Collins led the government-funded Human Genome Project, and he became deeply involved in Hitchens’ care.

In this video, aside from responding to the question, “Well Christopher, how are you feeling,” with “Well, I’m dying, but so are you,” Hitchens talks movingly about Collins, who he calls a great American, “one of the devout human beings I’ve ever met.”

Hitchens did find a drug that seemed to address one of his tumor’s mutations – it was reportedly Novartis’ Gleevec, the first targeted cancer drug – and that may have spared him some rounds of chemotherapy. But the medicine did not, of course, save him. Nor did it save Jobs.

According to Hitchens, Collins told him that he’s never seen anything in his medical career that could be called a miracle. That’s probably worth remembering as we begin to move into an era where many patients’ tumors will be sequenced. M.D. Anderson, where Hitchens died, has been trying to use DNA sequencing as a standard step in picking experimental drugs for patients; so have other cancer centers. One company, Foundation Medicine, which counts Google Ventures among its investors, is trying to turn this into a business model. Makers of DNA sequencing technology, including Illumina, Life Technologies, and Pacific Biosciences have been talking about the business opportunity for years.

This make sense because caring for late-stage cancer patients is so expensive, and so often futile, that even a costly technology like DNA sequencing (the price is dropping at an amazing rate but it’s still $5,000 or so for a full genome) could easily lead to improvements. But this technology is still in its early days, and it is not saving many lives just yet.

Genome Sequencing Reveals Previously Unreported Genetic Changes in Triple Negative Breast Tumors

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Posted 09 Dec 2011 — by James Street
Category Bioinformatics, Breast Cancer, Gene sequencing, genetic research, Triple Negative

First Genome Sequencing Clinical Trial for Triple Negative Disease Could Point to New Treatment Options, Results Presented at 2011 CTRC-AACR-San Antonio Breast Cancer Symposium

DALLAS, PHOENIX, and THE WOODLANDS, Texas, Dec. 8, 2011 /PRNewswire/ – Initial results from an ongoing clinical trial, the first designed to examine the utility of whole-genome sequencing for triple negative breast cancer, were reported today during the CRTC-AACR San Antonio Breast Cancer Symposium.

The results indicate activation of targets not previously associated with triple negative disease and could point toward new treatment strategies. Based on mutations uncovered by sequencing, physicians recommended the women enter treatment protocols for either existing drugs or new agents being evaluated in pharma-sponsored clinical trials.

Triple negative breast tumors, which make up nearly 20 percent of breast cancers, do not respond to treatment with targeted therapies such as Herceptin® (trastuzumab).

Of eleven tumors sequenced to date, each was genomically unique, but commonalities were observed.  Some patients displayed amplified genes in the RAS pathway; one patient had amplification of the BRAF oncogene, as well as activation of a growth pathway known as the MEK/AKT pathway. This patient displayed an impressive response to a MEK/AKT inhibitor currently in a phase I clinical study.

“Those results are quite striking considering that these are women with advanced disease,” said Joyce O’Shaughnessy, M.D., who presented the data.  “If MEK/AKT activation is found to be present in a substantial fraction of triple negative patients, inhibitors of this pathway could prove a significant tool in fighting this disease.”

Dr. O’Shaughnessy is medical director and co-chair of the Breast Cancer Research Committee, US Oncology Research; a practicing oncologist with Texas Oncology; and the Celebrating Women Chair of Breast Cancer Research at Baylor Charles A. Sammons Cancer Center.

“This is among the largest studies of a single tumor type in which whole genome sequencing is being used to identify potential options for targeted treatment,” said John Carpten, Ph.D., director of the Integrated Cancer Genomics Division at the Translational Genomics Research Institute (TGen). “As the field of genomic medicine matures, this study is sure to provide key early insights into how sequencing can best be utilized in the clinic.”

The study, titled “Next Generation Sequencing Reveals Co-Activating Events in the MAPK and PI3K/AKT Pathways in Metastatic Triple Negative Breast Cancers,” is sponsored by the Translational Genomics Research Institute (TGen) and US Oncology Research with support from Life Technologies Corporation. Whole-genome sequencing of tumors and normal tissue was performed on Life Technologies’ Applied Biosystems SOLiD™ platform, and results were validated in a CLIA-certified laboratory.

About Baylor Health Care System

Baylor Health Care System is a not-for-profit, faith-based supporting organization providing services to a network of acute care hospitals and related health care entities that provide patient care, medical education, research and community service. Baylor recorded more than 2.6 million patient encounters, $3.8 billion in total operating revenue, $4.4 billion in total assets and $513.5 million in community benefit in fiscal year 2010.  Baylor’s network of more than 300 access points includes 27 owned/operated/ ventured/affiliated hospitals, 23 joint ventured ambulatory surgical centers, 50 satellite outpatient locations, four senior centers and 156 HealthTexas Provider Network physician clinics.

About Texas Oncology

Texas Oncology delivers high-quality cancer care with leading-edge technology and advanced treatment and therapy options available to help patients achieve “More breakthroughs. More victories.”® in their fights against cancer. Texas Oncology, a pioneer in community-based cancer care, is an independent oncology practice with sites of service throughout Texas and southeastern Oklahoma. Texas Breast Specialists and Texas Urology Specialists, which focus on all areas of breast and urologic care, are a part of Texas Oncology.

Texas Oncology patients have the opportunity to take part in some of the most promising clinical trials in the nation for a broad range of cancers. Texas Oncology participates in innovative clinical trials from Phase I through Phase IV through US Oncology Research, which has helped to develop 43 FDA approved cancer therapies.

Texas Oncology is united in healing with The US Oncology Network, one of the nation’s largest community-based cancer treatment and research networks focused on advancing cancer care in America. As an affiliate of The US Oncology Network, Texas Oncology is united with more than 1,000 physicians and 10,000 cancer professionals nationwide. The US Oncology Network is supported by McKesson Specialty Health.

For more information, visit www.TexasOncology.com or call 1-888-864-I CAN (4226).

About TGen

The Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research for life changing results.  Research at TGen is focused on helping patients with diseases such as cancer, neurological disorders and diabetes. TGen is on the cutting edge of translational research where investigators are able to unravel the genetic components of common and complex diseases. Working with collaborators in the scientific and medical communities, TGen believes it can make a substantial contribution to the efficiency and effectiveness of the translational process. TGen is affiliated with the Van Andel Research Institute in Grand Rapids, Michigan. For more information, visit: www.tgen.org.

About US Oncology Research

McKesson Specialty Health conducts clinical trials through US Oncology Research, which draws from a network of experienced investigators and dedicated clinical staff who specialize in Phase I through Phase IV oncology clinical trials. US Oncology Research serves more than 90 sites in over 250 locations managing more than 200 active trials at any given time. Physicians in the research network have enrolled more than 50,000 patients in over 1,200 trials since inception in 1992 and have contributed to the development of 43 cancer therapies approved by the FDA. For more information call (800) 482-6700, option 4 or visit www.usoncology.com/oncologists.

(Logo: http://photos.prnewswire.com/prnh/20110216/MM49339LOGO)

Contacts:

Baylor Health Care System
Chris Callahan
Sr. Marketing and PR Consultant
(214) 820-6994 (Direct)
(214) 820-3055 (Office)
chris.callahan@baylorhealth.edu

Texas Oncology
Shana Bristow
214-665-1316
shana.bristow@fleishman.com

Translational Genomics Research Institute
Steve Yozwiak
Senior Science Writer
602-343-8704
syozwiak@tgen.org

US Oncology Research and Texas Oncology
Claire Crye
281-863-6783
281-825-9927
claire.crye@mckesson.com

NYT: Data bottleneck stymies genomics progress

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Posted 05 Dec 2011 — by James Street
Category Bioinformatics

Biotech computing scribes write about the logjam of genomics data from high-speed sequencing machines on a regular basis, but the problem somehow seems more acute when The New York Times‘ Andrew Pollack details the issue in one of the world’s most important newspapers, as he did Nov. 30.

It might sting even those familiar with the problem to read in the story that BGI, the world’s largest sequencing outfit, routinely stores genome data on computer disks and sends them to customers via FedEx because transferring the deluge of data over the Internet would take weeks. C. Titus Brown, a bioinformatics specialist at Michigan State, told Pollack that it’s “essentially impossible at the moment” to do a deep analysis on the huge amount of sequencing data from the Human Microbiome Project.

Experts project the data bottleneck to get worse with exponential growth in the number of sequenced genomes every year, and, as Pollock notes, some bioinformatics companies such as Google Ventures-backed DNAnexus, DNAstar and others have a viable market opportunity to seize. While covering promising genomic data analysis companies, the article doesn’t say much in the way of solutions to the need to use snail mail to transport data on sequenced genomes.

Dr. Patrick Soon-Shiong, a biotech tycoon who made billions on the sale of drug developers, is backing the National LambdaRail (NLR), the 12,000-mile fiber-optic network that enables high-speed data transfers of 100 gigabits per second, aiming to tap that infrastructure to support sharing of genomics data among researchers to speed the discovery of new treatments. Soon-Shiong’s recently formed nonprofit is also tackling the analysis piece with a supercomputer and data centers that are expected to eventually be linked to the NLR to be shared among scientists and clinicians.

While billionaires throw money and resources at the problem, there seems to be a lot of fertile ground to invent IT solutions to fix the mess. Us biotech-computing scribes at FierceBiotechIT will be keeping track of them.

 

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