Category Archives: Gene Medicine

CAMBRIDGE, Mass. & CHICAGO--(BUSINESS WIRE)--

Foundation Medicine, Inc., a molecular information company that brings comprehensive cancer genomic analysis to routine clinical care, today announced results from two studies using next-generation sequencing (NGS) to provide actionable information about genomic tumor alterations in individual patients cancers across all solid tumor types. The studies, being presented this week in an oral and poster session at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO), provide new evidence of the important role and clinical impact of NGS in cancer treatment.

These data follow Foundation Medicines recent launch of FoundationOne, the first pan-cancer, fully informative genomic profile for all solid tumors.

These studies, along with other results previously presented and published, provide unequivocal evidence of the significant clinical value of NGS-based comprehensive genomic analysis, said Michael J. Pellini, president and chief executive officer, Foundation Medicine. One test, using a very small amount of tissue, can enable physicians to tailor treatment to a patients molecular subtype. With our pan-cancer genomic profile now commercially available, physicians will have a critical decision-making tool to assist them in making the most appropriate therapeutic choices for their patients with cancer.

The first study, Discovery of Recurrent KIF5B-RET Fusions and Other Targetable Alterations from Clinical NSCLC Specimens (Abstract # 7510), was completed in collaboration with researchers at Dana-Farber Cancer Institute and assayed cancer-relevant genes in 24 cases of non-small cell lung cancer (NSCLC). Highlights of the analysis include:

Many non-small cell lung cancers have oncogenic alterations that may be sensitive to a targeted therapeutic approach, which can lead to better outcomes for individual patients, said Marzia Capelletti, Ph.D., Research Fellow in Medicine, Dana-Farber Cancer Institute. The challenge for physicians is to comprehensively understand the patients cancer by characterizing the genomic profile and develop a rational treatment strategy. The results of this study clearly demonstrate that there is a need to have a reliable tool to identify the particular molecular drivers of a tumor to help select appropriate therapies for individual patients.

An additional study, Next-Generation Sequencing Reliably Identifies Actionable Genomic Changes in Common and Rare Solid Tumors: The FMI Experience with the Initial 50 Consecutive Patients (Abstract #10590), utilized NGS to identify actionable genomic alterations across a variety of solid tumors in the first 304 clinical specimens (poster updated with clinical experience through May 1, 2012) analyzed by Foundation Medicines CLIA-approved laboratory. Alterations were defined as actionable if linked to an approved therapy in the tumor under study or another solid tumor; a known or suspected contraindication to a given therapy; or a clinical trial linked to the alteration. Lung, breast, colorectal, ovarian and pancreatic cancers were the most common solid tumors identified among 16 primary tumor types. In the analysis:

The complex nature of cancer and the transformation of cancer care, prompted by advanced understanding of genomic subtypes and emergence of targeted therapies, make the detection of alterations to guide therapeutic decision-making more critical than ever, said Gary Palmer, M.D., J.D., M.P.H., senior vice president of medical affairs and commercial development, Foundation Medicine, and lead author of the study. This NGS assay makes it possible for clinicians to make the best possible therapeutic choices, minimize the use of ineffective therapies and enhance enrollment in clinical trials appropriate for the individual patient.

Foundation Medicines first commercial offering, FoundationOne, is a fully informative genomic profile that allows any oncologist to use the same technology that informed the studies presented here as a clinical decision making tool in their own practice. FoundationOne uses routine, formalin-fixed, paraffin-embedded tumor samples. Test results are provided in a straightforward report that matches detected patients genomic alterations with potential treatment options and clinical trials.

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Foundation Medicine Announces New Data Using Next-Generation Sequencing to Detect Cancer-Related Mutations Not ...

ScienceDaily (June 1, 2012) Type 2 diabetes is popularly associated with obesity and a sedentary lifestyle. However, just as there are obese people without type 2 diabetes, there are lean people with the disease.

It has long been hypothesised that type 2 diabetes in lean people is more 'genetically driven'. A new study from a research team led by the Peninsula College of Medicine and Dentistry (PCMD), University of Exeter, which involved research institutions from around the world, has for the first time proved that lean type 2 diabetes patients have a larger genetic disposition to the disease than their obese counterparts. The study has also identified a new genetic factor associated only with lean diabetes sufferers.

The study is published in PLoS Genetics.

Using genetic data from genome-wide association studies, the research team tested genetic markers across the genome in approximately 5,000 lean patients with type 2 diabetes, 13,000 obese patients with the disease and 75,000 healthy controls.

The team found differences in genetic enrichment between lean and obese cases, which support the hypothesis that lean diabetes sufferers have a greater genetic predisposition to the disease. This is in contrast to obese patients with type 2 diabetes, where factors other than type 2 diabetes genes are more likely to be responsible. In addition, genetic variants near the gene, LAMA1, were linked to type 2 diabetes risk for the first time, with an effect that appeared only in the lean patients.

Dr. John Perry, one of the lead authors of the study, said: "Whenever a new disease gene is found, there is always the potential for it to be used as a drug target for new therapies or as a biomarker, but more work is needed to see whether or not this new gene has that potential."

He added: "This is the first time that a type 2 diabetes gene has been found to act in this way -- we do not know why it should be associated in one sub-group of patients and not another. It could point to the fact that type 2 diabetes may not be one disease, but may represent a number of subgroups. Again, more work is required to prove this hypothesis."

Dr. Perry concluded: "This study is a truly international one, bringing together research teams from around the world and leading UK institutions such as the University of Oxford, the University of Cambridge, King's College London, the University of Dundee and the University of Edinburgh."

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'Jack Spratt' diabetes gene identified

ScienceDaily (May 31, 2012) When flies are made to lose a gene with links to Restless Legs Syndrome (RLS), they suffer the same sleep disturbances and restlessness that human patients do. The findings reported online on May 31 in Current Biology, a Cell Press publication, strongly suggest a genetic basis for RLS, a condition in which patients complain of an irresistible urge to move that gets worse as they try to rest.

"Although widely prevalent, RLS is a disorder whose pathophysiological basis remains very poorly understood," said Subhabrata Sanyal of Emory University School of Medicine. "The major significance of our study is to highlight the fact that there might be a genetic basis for RLS. Understanding the function of these genes also helps to understand and diagnose the disease and may offer more focused therapeutic options that are currently limited to very general approaches."

Sanyal's team recognized that a number of genome-wide association studies in humans had suggested connections between RLS and variation in a single gene (BTBD9).

"BTBD9 function or its relationship to RLS and sleep were a complete mystery," Sanyal said.

His team realized that there might be a way to shed some light on that mystery in fruit flies. Flies have a single, highly conserved version of the human BTBD9. They decided to test whether the gene that had turned up in those human studies would have any effect on sleep in the insects. In fact, flies need sleep just like humans do, and their sleep patterns are influenced by the same kinds of brain chemistry.

The researchers now report that flies lacking their version of the RLS-associated gene do lose sleep as they move more. When those flies were treated with a drug used for RLS, they showed improvements in their sleep.

The studies also yielded evidence about how the RLS gene works by controlling dopamine levels in the brain as well as iron balance in cells. Sanyal said his team will continue to explore other RLS-related genes that have been identified in human studies in search of more details of their interaction and function.

"Our results support the idea that genetic regulation of dopamine and iron metabolism constitute the core pathophysiology of at least some forms of RLS," the researchers write.

More broadly, they say, the study emphasizes the utility of simple animals such as fruit flies in unraveling the genetics of sleep and sleep disorders.

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Flies with restless legs syndrome point to a genetic cause

Category: Science & Technology Posted: June 1, 2012 04:59AM Author: Guest_Jim_*

A future with a failing body is not something anyone looks forward to, so researchers are looking for ways to control the process. We already have medications and treatments so senior citizens can stay active with each passing year, but researchers are still working towards a way to stop or completely reverse the aging process itself.

Studies have discovered that as people age, the telomeres at the ends of their chromosomes fall off. Preventing this from happening inhibits aging, but can also cause cancer, which is an unchecked and uncontrolled mutation of normal cells. Researchers have known that inflammation is also connected to aging and cancer, but did not know how these three, seemingly unconnected, things were intertwined. Those at NYU Langone Medical Center / New York University School of Medicine have discovered that the link is through the AUF1 gene.

This gene controls inflammation by turning off that natural response before septic shock can occur. What the researchers discovered is that AUF1 also triggers the activation of telomerase, an enzyme that repairs telomeres, or kills cells by not activating, to repair the telomeres. This one gene regulates inflammation, can prevent accelerated aging, and prevent cancer by not activating telomerase. The researchers' next step is to examine the human population to see if mutations of the AUF1 gene are linked to different diseases.

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Inflammation, Aging and Cancer All Linked to One Gene

Public release date: 31-May-2012 [ | E-mail | Share ]

Contact: Holly Korschun hkorsch@emory.edu 404-727-3990 Emory University

Scientists have discovered that mutations in the gene BTBD9, which is linked with restless legs syndrome (RLS) in humans, disturb sleep in fruit flies. The mutant flies wake up more often during sleep periods, which resembles a key feature of human RLS.

The same mutations in BTBD9 also reduce levels of the neurotransmitter dopamine in the flies. Some kind of deficiency in dopamine signaling is thought to lie behind RLS in humans.

The results are published in the journal Current Biology.

"Flies and humans are distant from each other on the evolutionary tree, yet the same gene seems to be regulating a fundamental process in both organisms and affecting how soundly they sleep," says senior author Subhabrata Sanyal, PhD, assistant professor of cell biology at Emory University School of Medicine.

People with RLS experience unpleasant sensations in their legs and urges to move them, interfering with the ability to sleep. Genetics plays a major role in RLS, and most people with RLS have a close family member with the disorder. A variant in the BTBD9 gene accounts for about half of the risk for RLS in the population, according to multiple genetic studies (http://1.usa.gov/LqrO5L).

While medications exist to treat RLS, in some patients they are ineffective or have side effects. Researchers don't have a good understanding of what is going wrong in the nervous system in people affected by RLS, or what the BTBD9 gene does. Studying the fly version of BTBD9 could shed light on the basic biology and eventually lead to improved treatments for humans.

Postdoctoral fellow Amanda Freeman, the first author of the paper, examined flies' sleep behavior by putting individual flies into tubes with infrared sensors, which can detect when a fly moves across the middle of the tube. If a fly doesn't cross the beam for five minutes, it's considered asleep. She found that the BTBD9 mutant flies woke up more often during the night.

Disabling BTBD9 also makes flies more mobile while awake. Mutant flies confined in a tube move back and forth more often, leading Freeman and Sanyal to dub the mutant flies "wanderlust."

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Restless legs syndrome in fruit flies: Mutation in fly version of a human RLS gene disturbs sleep

Newswise The same gene variations that make it difficult to stop smoking also increase the likelihood that heavy smokers will respond to nicotine-replacement therapy and drugs that thwart cravings, a new study shows.

The research, led by investigators at Washington University School of Medicine in St. Louis, will appear online May 30 in the American Journal of Psychiatry.

The study suggests it may one day be possible to predict which patients are most likely to benefit from drug treatments for nicotine addiction.

Smokers whose genetic makeup puts them at the greatest risk for heavy smoking, nicotine addiction and problems kicking the habit also appear to be the same people who respond most robustly to pharmacologic therapy for smoking cessation, says senior investigator Laura Jean Bierut, MD, professor of psychiatry. Our research suggests that a persons genetic makeup can help us better predict who is most likely to respond to drug therapy so we can make sure those individuals are treated with medication in addition to counseling or other interventions.

For the new study, the researchers analyzed data from more than 5,000 smokers who participated in community-based studies and more than 1,000 smokers in a clinical treatment study. The scientists focused on the relationship between their ability to quit smoking successfully and genetic variations that have been associated with risk for heavy smoking and nicotine dependence.

People with the high-risk genetic markers smoked an average of two years longer than those without these high-risk genes, and they were less likely to quit smoking without medication, says first author Li-Shiun Chen, MD, assistant professor of psychiatry at Washington University. The same gene variants can predict a persons response to smoking-cessation medication, and those with the high-risk genes are more likely to respond to the medication.

In the clinical treatment trial, individuals with the high-risk variants were three times more likely to respond to drug therapy, such as nicotine gum, nicotine patches, the antidepressant buproprion and other drugs used to help people quit.

Tobacco use is the leading cause of preventable illness and death in the United States and a major public health problem worldwide. Cigarette smoking contributes to the deaths of an estimated 443,000 Americans each year. Although lung cancer is the leading cause of smoking-related cancer death among both men and women, tobacco also contributes to other lung problems, many other cancers and heart attacks.

Bierut and Chen say that the gene variations they studied are not the only ones involved in whether a person smokes, becomes addicted to nicotine or has difficulty quitting. But they contend that because the same genes can predict both heavy smoking and enhanced response to drug treatment, the genetic variants are important to the addiction puzzle.

Its almost like we have a corner piece here, Bierut says. Its a key piece of the puzzle, and now we can build on it. Clearly these genes arent the entire story other genes play a role, and environmental factors also are important. But weve identified a group thats responding to pharmacologic treatment and a group thats not responding, and thats a key step in improving, and eventually tailoring, treatments to help people quit smoking.

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Genes Predict if Medication Can Help You Quit Smoking