Crowd control: Nearly 4 percent of people carry at least one genetic variant tied to a serious medical condition.

brainmaster / Getty Images

Most adults with genetic variants tied to certain conditions, such as heart disease or cancer, go undiagnosed, according to a study of more than 50,000 people1.

The variants silence leaves these people unaware of their risk of developing the conditions later in life, says lead investigator David Carey, director of the Weis Center for Research at Geisinger Health System in Danville, Pennsylvania.

Careys team looked for genetic variants associated with 27 chronic conditions. The list of conditions does not include autism, but does include tuberous sclerosis complex. As many as half of all people with tuberous sclerosis complex have autism. Other teams are studying the same population to gauge the effects of variants linked to autism.

The value lies in the huge population, all captured within the same healthcare system. Its really fantastic, says Dan Arking, associate professor of genetic medicine at Johns Hopkins University in Baltimore, Maryland, who was not involved in the new work.

The variants in the study are clinically significant: Some increase the risk of the linked condition by up to 70 percent. But variants interact with many other genetic and environmental factors, and these interactions may cause the conditions features to be more or less severe or even absent.

People used to say anytime there is a [spontaneous] variant or something really rare, that it must cause disease, says Arking. The new study instead suggests that, on the contrary, some rare variants have weak ties to conditions such as autism, he says. The results appeared 23 December in Science2.

Carey and his team looked at data from the MyCode Community Health Initiative, launched in 2007 by Geisinger Health System in central Pennsylvania. MyCode researchers have collected DNA samples and up to 14 years worth of medical records from the participants.

The researchers probed the 50,726 participants genomes for inserted or deleted sequences, and for single nucleotide variants, called SNVs, in the code. Their analysis revealed that each individual harbors about 21,409 SNVs, consistent with findings from previous studies.

The researchers then narrowed their analysis to 76 genes known to contribute to life-threatening conditions such as cancer or cardiovascular disease. The list includes three genes tied to tumor growth and to autism: PTEN, TSC1 and TSC2. (Clinicians are obligated to counsel individuals with variants in any of these 76 genes.)

Nearly 4 percent of the general population carries variants in at least one of these genes, the researchers found. But more than one-third of these people show no symptoms and have no family history of the linked condition. For example, most of the individuals who carry a variant linked to an inherited condition that causes high cholesterol have normal cholesterol levels, according to a second study by Careys team in the same issue of Science.

The findings could mean the individual will develop the condition later in life or not, Carey says. Other variants in her genome might mitigate the risk, he says.

We generally look at one gene at a time, but we have about 20,000 genes and they all work in concert, Carey says. Were not sophisticated enough yet to be able to tease out all the genetic interactions, but we know that they exist.

Last year, another team of researchers used the MyCode data to show that genetic changes tied to autism also crop up in many people without the condition. At the 2016 American Society of Human Genetics annual meeting in Vancouver, Canada, last year, they presented results showing that about 2,000 of the MyCode participants carry large deletions or duplications of genetic material associated with autism, intellectual disability or schizophrenia. But less than 5 percent of this group has received treatment for any of the conditions.

The finding suggests that genetic variants can confer features so subtle that they go unrecognized well into adulthood. Researchers could study this group to understand the mildest end of the autism spectrum.

This cohort could help us describe the full picture of autism, the breadth of the phenotype, says Christa Lese Martin, director of the Autism and Developmental Medicine Institute at Geisinger Health System in Lewisburg, Pennsylvania. Martin was a lead investigator on the autism study but was not involved in the new work.

About 125,000 people have enrolled in MyCode so far. By early next year, researchers expect to have sequencing data for 90,000 of the individuals.

Read the original here:
Many people with harmful genetic variants show no ill effects - Spectrum

Public release date: 16-Oct-2012 [ | E-mail | Share ]

Contact: Tina McDowell tmcdowell@carnegiescience.edu 202-929-1120 Carnegie Institution

Washington, D.C.The Carnegie Institution for Science and the University of Massachusetts Medical School (UMMS) have been granted United States Patent 8,283,329, entitled, "Genetic inhibition of double-stranded RNA." The patent, issued on October 9, 2012, is broadly directed to the use of RNA interference (RNAi) to inhibit expression of a target gene in animal cells, including mammalian cells.

The process by which RNA, the cellular material responsible for the transmission of genetic information, can silence a targeted gene within a living cell was discovered in 1998 by Carnegie's Andrew Fire, (now a professor at Stanford University) and Craig C. Mello, Howard Hughes Medical Institute Investigator, Blais University Chair in Molecular Medicine and distinguished professor of molecular medicine and cell & developmental biology at UMass Medical School. The duo received the 2006 Nobel Prize in Physiology and/or Medicine for this work.

Already a powerful research tool used to isolate and identify genes and their function in the laboratory, RNAi holds the promise of shutting down disease-causing genes in humans and has broad implications for the development of new treatments and drugs for a range of diseases, including cancer. Researchers around the globeincluding UMass Medical School and the Carnegie Institutionare investigating novel methods for synthesizing and delivering RNAi molecules able to turn off disease-causing genes to human cells. According to the patent, the double-stranded RNA (ds-RNA) responsible for the RNAi process may be either synthesized by the animal cell, or otherwise provided to the cell, in an amount sufficient to inhibit expression of the target gene.

The single-stranded RNA molecule is commonly known for its role in shuttling the genetic code contained in DNA from the cell's nucleus to its ribosomes where proteins are made, and for making sure that the proteins are correctly constructed to perform their functions in living organisms. In RNAi, the first strand of double-stranded RNA molecule has the ribonucleotide sequence that matches the nucleotide sequence in the targeted gene (also called sense); the second strand of RNA has a complementary sequence to that in the target gene (called antisense). When introduced to an organism, the double stranded RNA degrades a specific messenger RNA (mRNA) molecule, which disrupts the message-carrying process and inactivates the gene, essentially halting the progression of an invading viral infection or, for example, tumor growth.

"We are very pleased that the United States Patent and Trademark Office has issued this broad patent for the groundbreaking work of Dr. Mello and Dr. Fire," said James P. McNamara, Executive Director of the Office of Technology Management of the University of Massachusetts Medical School. "RNA interference is a tremendously promising tool with enormous potential for treating disease. Our hope is to see the further advancement of the RNAi field toward novel therapies in the public interest."

"We are very pleased that the patent office has granted a patent of the present scope for such a fundamental advance," said Richard A. Meserve, president of the Carnegie Institution. "The research exemplifies what Andrew Carnegie sought to accomplishto benefit humankind."

The current patent is the most recent of several patents resulting from this work.

###

Read more:
Carnegie Institution and UMass Medical School granted broad US Patent related to RNA interference

Dutch biotech company uniQure said Monday it would start selling the first human gene therapy to be approved in the West by mid-2013 and predicted an explosion of similar therapies to come.

The European Commission approved Glybera on October 25, making the drug for treating the extremely rare disorder lipoprotein lipase deficiency (LPLD) the first to be approved for sale in Europe or North America.

"We believe that after Glybera's approval gene therapy is at the beginning of a period of rapid growth similar to the development of the antibody business in the last decade," uniQure chief executive Joern Aldag said in a statement.

Gene therapy works by modifying a patient's DNA to combat a specific disease, and has been experimented with to treat everything from blindness to depression and brain wasting diseases.

But the relatively unknown treatments have struggled to obtain regulatory approval in the West, although authorities in China approved a gene therapy for treating head and neck cancer as long ago as 2003.

Gene medicine burst on the medical scene in the late 1990s and is one of the most alluring areas of biotechnology, offering the theoretical promise of blocking or reversing inherited disease.

But this new frontier has also been hit by occasional setbacks, notably an unexpected or uncontrollable response from the immune system.

So far, successes have been few, limited to single-gene disorders -- as opposed to complex multi-gene disorders that account for the commonest diseases.

Setbacks included the tragic death of an 18-year-old US volunteer, Jesse Gelsinger, in 1999, and the development of cancer among two French children treated for "bubble baby" syndrome, a chronic lack of immune defences.

Glybera treats LPLD, an inherited disease that affects around one or two people in a million, by preventing them from metabolising certain fat particles in the blood.

Read the original:
First gene therapy to go on sale in Europe in 2013: company

Public release date: 16-Oct-2012 [ | E-mail | Share ]

Contact: Anne DeLotto Baier abaier@health.usf.edu 813-974-3303 University of South Florida (USF Health)

Tampa, FL (Oct. 16, 2012) -- A landmark paper identifying genetic signatures that predict which patients will respond to a life-saving drug for treating congestive heart failure has been published by a research team co-led by Stephen B. Liggett, MD, of the University of South Florida.

The study, drawing upon a randomized placebo-controlled trial for the beta blocker bucindolol, apprears this month in the online international journal PLoS ONE. In addition to Dr. Liggett, whose laboratory discovered and characterized the two genetic variations, Christopher O'Connor, MD, of Duke University Medical Center, and Michael Bristow, MD, PhD, of ARCA biopharma and the University of Colorado Anschutz Medical Campus, were leading members of the research team.

The analysis led to a "genetic scorecard" for patients with congestive heart failure, a serious condition in which the heart can't pump enough blood to meet the body's needs, said Dr. Liggett, the study's co-principal investigator and the new vice dean for research and vice dean for personalized medicine and genomics at the USF Morsani College of Medicine.

"We have been studying the molecular basis of heart failure in the laboratory with a goal of finding genetic variations in a patient's DNA that alter how drugs work," Dr. Liggett said. "We took this knowledge from the lab to patients and found that we can indeed, using a two-gene test, identify individuals with heart failure who will not respond to bucindolol and those who have an especially favorable treatment response. We also identified those who will have an intermediate level of response."

The research has implications for clinical practice, because the genetic test could theoretically be used to target the beta blocker to patients the drug is likely to help. Equally important, its use could be avoided in patients with no likelihood of benefit, who could then be spared potential drug side effects. Prospective studies are needed to confirm that bucindolol would be a better treatment than other classes of beta blockers for a subset of patients with health failure.

Dr. Liggett collaborated with medical centers across the United States, including the NASDAq-listed biotech company ARCA biopharma, which he co-founded in Denver, CO. This genetic sub-study involved 1,040 patients who participated in the Beta-Blocker Evaluation of Survival Trial (BEST). The researchers analyzed mortality, hospital admissions for heart failure exacerbations and other clinical outcome indicators of drug performance.

"The results showed that the choice of the best drug for a given patient, made the first time without a trial-and-error period, can be accomplished using this two-gene test," Dr. Liggett said.

The genetic test discovered by the Liggett team requires less than 1/100th of a teaspoon of blood drawn from a patient, from which DNA is isolated. DNA is highly stable when frozen, so a single blood draw will suffice for many decades, Dr. Liggett said. And since a patient's DNA does not change over their lifetime, as new discoveries are made and other tests need to be run, it would not be necessary to give another blood sample, he added.

Read the original here:
2-gene test predicts which patients with heart failure respond best to beta-blocker drug

Published: Oct. 16, 2012 at 8:30 PM

EVANSTON, Ill., Oct. 16 (UPI) -- U.S. scientists say they've discovered how to control the shape of nanoparticles that can move DNA through the body to treat cancer and other diseases.

A gene therapy technique utilizing nanoparticles is significant in that it does not use a virus to carry DNA into cells, as some gene therapy strategies relying on viruses have posed health risks, researchers at Northwestern University and John Hopkins University reported.

"These nanoparticles could become a safer and more effective delivery vehicle for gene therapy, targeting genetic diseases, cancer and other illnesses that can be treated with gene medicine," John Hopkins material science Professor Hai-Quan Mao said.

Mao, who has been developing non-viral nanoparticles for gene therapy for a decade, said a major breakthrough is the ability to "tune" the particles in three shapes, resembling rods, worms and spheres, which mimic the shapes and sizes of viral particles.

The nanoparticles carry healthy snippets of DNA within protective polymer coatings and are designed to deliver their genetic payload only after they have moved through the bloodstream and entered the target cells, prompting the cells to produce functional proteins that combat disease.

More here:
Nanoparticles seen as gene therapy advance

ScienceDaily (Oct. 16, 2012) A landmark paper identifying genetic signatures that predict which patients will respond to a life-saving drug for treating congestive heart failure has been published by a research team co-led by Stephen B. Liggett, MD, of the University of South Florida.

The study, drawing upon a randomized placebo-controlled trial for the beta blocker bucindolol, appears this month in the international online journal PLoS ONE. In addition to Dr. Liggett, whose laboratory discovered and characterized the two genetic variations, Christopher O'Connor, MD, of Duke University Medical Center, and Michael Bristow, MD, PhD, of ARCA biopharma and the University of Colorado Anschutz Medical Campus, were leading members of the research team.

Dr. Stephen Liggett, who joined USF just four months ago to lead the University's Center for Personalized Medicine and Genomics, was a senior author of the paper.

The analysis led to a "genetic scorecard" for patients with congestive heart failure, a serious condition in which the heart can't pump enough blood to meet the body's needs, said Dr. Liggett, the study's co-principal investigator and the new vice dean for research and vice dean for personalized medicine and genomics at the USF Morsani College of Medicine.

"We have been studying the molecular basis of heart failure in the laboratory with a goal of finding genetic variations in a patient's DNA that alter how drugs work," Dr. Liggett said. "We took this knowledge from the lab to patients and found that we can indeed, using a two-gene test, identify individuals with heart failure who will not respond to bucindolol and those who have an especially favorable treatment response. We also identified those who will have an intermediate level of response." The research has implications for clinical practice, because the genetic test could theoretically be used to target the beta blocker to patients the drug is likely to help. Equally important, its use could be avoided in patients with no likelihood of benefit, who could then be spared potential drug side effects. Prospective studies are needed to confirm that bucindolol would be a better treatment than other classes of beta blockers for a subset of patients with health failure.

Dr. Liggett collaborated with medical centers across the United States, including the NASDAq-listed biotech company ARCA biopharma, which he co-founded in Denver, CO. This genetic sub-study involved 1,040 patients who participated in the Beta-Blocker Evaluation of Survival Trial (BEST). The researchers analyzed mortality, hospital admissions for heart failure exacerbations and other clinical outcome indicators of drug performance.

"The results showed that the choice of the best drug for a given patient, made the first time without a trial-and-error period, can be accomplished using this two-gene test," Dr. Liggett said.

The genetic test discovered by the Liggett team requires less than 1/100th of a teaspoon of blood drawn from a patient, from which DNA is isolated. DNA is highly stable when frozen, so a single blood draw will suffice for many decades, Dr. Liggett said. And since a patient's DNA does not change over their lifetime, as new discoveries are made and other tests need to be run, it would not be necessary to give another blood sample, he added.

This is part of the strategy for the USF Center for Personalized Medicine and Genomics. The discovery of genetic variations in diseases can be targeted to predict three new types of information: who will get a disease, how the disease will progress, and the best drug to use for treatment.

"In the not too distant future, such tests will become routine, and patient outcomes, and the efficiency and cost of medical care will be impacted in positive ways. We also will move toward an era where we embrace the fact that one drug does not fit all," Dr. Liggett said. "If we can identify by straightforward tests which drug is best for which patient, drugs that work with certain smaller populations can be brought to the market, filling a somewhat empty pipeline of new drugs."

Follow this link:
Two-gene test predicts which patients with heart failure respond best to beta-blocker drug

Reported by Julielynn Wong, MD

A single gene may shed light on why more than half of transplanted kidneys fail in 10 years, a new study found.

The study of nearly 4,500 European transplant recipients, some whom were followed for 20 years, found kidneys with one version of the gene were 69 percent more likely to fail, sending patients back to dialysis and a transplant waiting list.

But with a wait list 74,000 names long and only17,500 kidneys donated annually, doctors wont be excluding any organs based on the gene variant just yet.

We just dont have enough donor kidneysto go around now, said Dr. Michael E. Shapiro, associate professor of surgery at New Jersey Medical School/University of Medicine and Dentistry New Jersey, who was not involved in the study. So wecouldntexclude such kidneys based solely on genetic variation.

The study authors are unsure why the gene variant is linked to a higher risk of kidney failure after a transplant, but they suspect it might have to do with the anti-rejection drugs needed to prevent the immune system from attacking the new organ. Those drugs can cause kidney failure if they accumulate in high levels, they said.

But because kidneys are such a rare and valuable resource, even those more likely to fail in the long run will continue to be transplanted. The alternative is dialysis, a process that artificially filters blood, according to Dr. Stanley Jordan, medical director of the Kidney Transplant Program at Cedars-Sinai Medical Center in Los Angeles, who was not involved with the study.

And dialysis has its drawbacks.

We know that remaining on dialysis has a very high mortality rate, as high as 20 percent per year for some patients, said Jordan.

Dialysis costs roughly $85,000 per year, compared with $19,000 per year for a working transplanted kidney, Jordan said, citing a 2011 report on the United States Renal Data System website. But the cost of treating a failed kidney transplant can be as high as $230,000 in the first year, with Medicare usually bearing the brunt of these costs, he added.

Original post:
Gene Linked to Kidney Failure

Public release date: 15-Oct-2012 [ | E-mail | Share ]

Contact: Anita Srikameswaran 412-578-9193 University of Pittsburgh Schools of the Health Sciences

PITTSBURGH, Oct. 15, 2012 An increased risk of autism spectrum disorders (ASD) could result from an accumulation of many small, common genetic variations rather than large-effect, rare changes in the genetic code, according to a multicenter team led by researchers at the University of Pittsburgh School of Medicine. Their findings, published today in Molecular Autism, provide new insights into the genetic factors that underlie the neurodevelopmental condition.

Scientists have debated about the genetic contributions that lead to ASD in families where only one individual is affected, called simplex, versus those that have multiple affected family members, called multiplex, said senior author Bernie Devlin, Ph.D., associate professor, Department of Psychiatry, University of Pittsburgh School of Medicine.

"Our team compared simplex, multiplex and unaffected families using sophisticated quantitative genetic techniques," he said. "In families where only one child has an ASD, 40 percent of the risk is inherited while in families with more than one affected child, the risk rises to 60 percent."

For the project, the team examined thousands of DNA samples from families in the Simons Simplex Collection, in which one child but no parent or sibling had an ASD; the Autism Genome Project, in which more than one child had an ASD; and unaffected families enrolled in the HealthABC Program.

In addition to reviewing nearly 1 million gene variations, called single nucleotide polymorphisms (SNPs), to look for inheritance patterns associated with ASD, they also ran computer simulations to plot family trees using 1,000 SNPs that appear to impact the risk of ASD.

"These small gene changes can add up even though individually they do little harm," Dr. Devlin said. "This might explain why parents who do not have autism traits can have children who do."

Other research has shown that autism and related disorders also can arise from spontaneous variations in parental genes prior to conception as well as rare mutations of larger effect that are passed on, he noted. The multiple inheritance patterns could help explain the range of symptoms in the disorder.

The team included researchers from Yale University, the University of Michigan, University of California Los Angeles, Emory University, Harvard University and others. The effort was funded by grants from the Simons Foundation and National Institutes of Health grant MH057881.

Visit link:
Additive effect of small gene variations can increase risk of autism spectrum disorders

ScienceDaily (Oct. 12, 2012) Researchers from Johns Hopkins and Northwestern universities have discovered how to control the shape of nanoparticles that move DNA through the body and have shown that the shapes of these carriers may make a big difference in how well they work in treating cancer and other diseases.

This study, to be published in the Oct. 12 online edition of the journal Advanced Materials, is also noteworthy because this gene therapy technique does not use a virus to carry DNA into cells. Some gene therapy efforts that rely on viruses have posed health risks.

"These nanoparticles could become a safer and more effective delivery vehicle for gene therapy, targeting genetic diseases, cancer and other illnesses that can be treated with gene medicine," said Hai-Quan Mao, an associate professor of materials science and engineering in Johns Hopkins' Whiting School of Engineering.

Mao, co-corresponding author of the Advanced Materials article, has been developing nonviral nanoparticles for gene therapy for a decade. His approach involves compressing healthy snippets of DNA within protective polymer coatings. The particles are designed to deliver their genetic payload only after they have moved through the bloodstream and entered the target cells. Within the cells, the polymer degrades and releases DNA. Using this DNA as a template, the cells can produce functional proteins that combat disease.

A major advance in this work is that Mao and his colleagues reported that they were able to "tune" these particles in three shapes, resembling rods, worms and spheres, which mimic the shapes and sizes of viral particles. "We could observe these shapes in the lab, but we did not fully understand why they assumed these shapes and how to control the process well," Mao said. These questions were important because the DNA delivery system he envisions may require specific, uniform shapes.

To solve this problem, Mao sought help about three years ago from colleagues at Northwestern. While Mao works in a traditional wet lab, the Northwestern researchers are experts in conducting similar experiments with powerful computer models.

Erik Luijten, associate professor of materials science and engineering and of applied mathematics at Northwestern's McCormick School of Engineering and Applied Science and co-corresponding author of the paper, led the computational analysis of the findings to determine why the nanoparticles formed into different shapes.

"Our computer simulations and theoretical model have provided a mechanistic understanding, identifying what is responsible for this shape change," Luijten said. "We now can predict precisely how to choose the nanoparticle components if one wants to obtain a certain shape."

The use of computer models allowed Luijten's team to mimic traditional lab experiments at a far faster pace. These molecular dynamic simulations were performed on Quest, Northwestern's high-performance computing system. The computations were so complex that some of them required 96 computer processors working simultaneously for one month.

In their paper, the researchers also wanted to show the importance of particle shapes in delivering gene therapy. Team members conducted animal tests, all using the same particle materials and the same DNA. The only difference was in the shape of the particles: rods, worms and spheres.

Go here to read the rest:
Shape matters in DNA nanoparticle therapy: Particles could become a safer, more effective delivery vehicle for gene ...

By Traci Pedersen Associate News Editor Reviewed by John M. Grohol, Psy.D. on October 11, 2012

Researchers have pinpointed a small region in the genome the entirety of human hereditary information as a vital factor in the development of psychiatric disease and obesity.

Brain-derived neurotrophic factor, or BDNF, is a nervous system growth factor that plays a critical role in brain development. To determine the role of BDNF in humans, McGill researchers screened over 35,000 people referred for genetic screening at clinics, as well as over 30,000 control subjects in the U.S., Canada and Europe.

Researchers found five individuals with BDNF deletions, all of whom were obese, had a mild-moderate intellectual impairment, and had a mood disorder.

The children had anxiety disorders, aggressive disorders, or attention deficit-hyperactivity disorder (ADHD), while post-pubescent individuals had anxiety and major depressive disorders. Subjects slowly gained weight with age, suggesting that obesity is a long-term process when BDNF is deleted.

The results of the new study, published in the Archives of General Psychiatry, reveal for the first time the link between BDNF deletion, cognition, and weight gain in humans.

Scientists have been trying to find a region of the genome which plays a role in human psychopathology, searching for answers anywhere in our DNA that may give us a clue to the genetic causes of these types of disorders, saidCarl Ernst, Ph.D., from McGills Department of Psychiatry, Faculty of Medicine.

Our study conclusively links a single region of the genome to mood and anxiety.

Based on animal studies, BDNF has been a suspect of several functions in the brain, but no study has proven what happens when BDNF is missing from the human genome. The new study helps provide a better understanding of human behavior and mood by clearly identifying genes associated with mental disorders.

Mood and anxiety can be seen like a house of cards. In this case, the walls of the house represent the myriad of biological interactions that maintain the structure, said Ernst, who is also a researcher at the Douglas Mental Health University Institute.

Read more:
Gene Deletion Linked to Mental Illness, Obesity

Dundee University experts said P34 played a key role in causing the disease punctate PPK, which gives sufferers dots of hard, thickened skin which can cause pain and discomfort.

Irwin McLean, professor of human genetics in the Centre for Dermatology and Genetic Medicine at the university, said: "We have not only found this gene but we have been able to figure out how it works, which is very important.

"When the gene is disrupted or knocked out, the cells in the skin grow too fast and this results in these hard, thick, painful lesions which can be quite debilitating. When the gene is working properly then the skin forms normally.

"Knowing about this gene and what it does makes it easier for us to diagnose this form of skin disease and look towards developing new therapies.

"The pathway where this gene functions is a possible drug target although it will need more work to identify how we can take advantage of that."

Punctate PPK is one of a whole family of PPK skin diseases, each of which are relatively rare. It is estimated to affect around one in every 15,000 people in the UK.

The find was made possible by the use of next generation sequencing technology, which allows researchers to screen large amounts of genome data in a short space of time.

"This is a notable step forward in diagnosing skin diseases and the genetic causes behind them as this is research that we simply could not have done just a few years ago, We are now able to spot faulty genes and track their behaviour far more effectively," said Mr McLean.

The research is published in the journal Nature Genetics.

Contextual targeting label:

Read more here:
Gene clues to help tackle skin disease

Newswise Researchers from Mount Sinai School of Medicine have identified a six-gene signature that can be used in a test to predict survival in men with aggressive prostate cancer, according to new research published in the October issue of The Lancet Oncology. This is the first study to demonstrate how prognostic markers may be useful in a clinical setting.

Using blood from 202 men with treatment-resistant prostate cancer, researchers found six genes characteristic of treatment-resistant prostate cancer. Men with the six-gene signature were high-risk, with a survival time of 7.8 months, and men without it were low-risk, with a survival time of approximately 34.9 months. A replication study of 140 additional patients validated these findings. William K. Oh, MD, Chief of the Division of Hematology and Medical Oncology of The Tisch Cancer Institute at The Mount Sinai Medical Center, led the research team.

"There is an urgent need for predictive models that help assess how aggressive the disease is in prostate cancer patients, as survival can vary greatly," said Dr. Oh. "Our six-gene model, delivered in a simple blood test, will allow clinicians to better determine the course of action for their patients, determine clinical trial eligibility, and lead to more targeted studies in late-stage disease."

Until now, disease prognosis in advanced prostate cancer could only be determined through clinical predictors or, occasionally, tumor biopsies with only moderately predictive results. This study shows the efficacy of the six-gene model blood test in determining length of survival.

The genes noted in the model suggest possible changes in the immune system related to late-stage disease that warrant further study as a target for immune-based therapies, said Dr. Oh.

Dr. Ohs team is conducting additional studies exploring the feasibility of the six-gene signature in other types of prostate cancer, the stability of the signature during the course of a patients illness, and the predictive ability of this signature in patients with prostate cancer treated with immune-based therapies.

This work was done in collaboration with colleagues at Dana-Farber Cancer Institute in Boston and Memorial Sloan-Kettering Cancer Center in New York City.

About The Mount Sinai Medical Center The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of the leading medical schools in the United States. The Medical School is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by US News and World Report.

The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nations oldest, largest and most-respected voluntary hospitals. In 2011, US News and World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nations top hospitals based on reputation, safety, and other patient-care factors. Mount Sinai is one of 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and US News and World Report and whose hospital is on the US News and World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place. For more information, visit http://www.mountsinai.org/.

Find Mount Sinai on: Facebook: http://www.facebook.com/mountsinainyc Twitter: @mountsinainyc YouTube: http://www.youtube.com/mountsinainy

Go here to see the original:
Researchers Discover Gene Signature that Predicts Prostate Cancer Survival

Public release date: 10-Oct-2012 [ | E-mail | Share ]

Contact: Mount Sinai Press Office newsmedia@mssm.edu 212-241-9200 The Mount Sinai Hospital / Mount Sinai School of Medicine

Researchers from Mount Sinai School of Medicine have identified a six-gene signature that can be used in a test to predict survival in men with aggressive prostate cancer, according to new research published in the October issue of The Lancet Oncology. This is the first study to demonstrate how prognostic markers may be useful in a clinical setting.

Using blood from 202 men with treatment-resistant prostate cancer, researchers found six genes characteristic of treatment-resistant prostate cancer. Men with the six-gene signature were high-risk, with a survival time of 7.8 months, and men without it were low-risk, with a survival time of approximately 34.9 months. A replication study of 140 additional patients validated these findings. William K. Oh, MD, Chief of the Division of Hematology and Medical Oncology of The Tisch Cancer Institute at The Mount Sinai Medical Center, led the research team.

"There is an urgent need for predictive models that help assess how aggressive the disease is in prostate cancer patients, as survival can vary greatly," said Dr. Oh. "Our six-gene model, delivered in a simple blood test, will allow clinicians to better determine the course of action for their patients, determine clinical trial eligibility, and lead to more targeted studies in late-stage disease."

Until now, disease prognosis in advanced prostate cancer could only be determined through clinical predictors or, occasionally, tumor biopsies with only moderately predictive results. This study shows the efficacy of the six-gene model blood test in determining length of survival.

"The genes noted in the model suggest possible changes in the immune system related to late-stage disease that warrant further study as a target for immune-based therapies," said Dr. Oh.

Dr. Oh's team is conducting additional studies exploring the feasibility of the six-gene signature in other types of prostate cancer, the stability of the signature during the course of a patient's illness, and the predictive ability of this signature in patients with prostate cancer treated with immune-based therapies.

###

This work was done in collaboration with colleagues at Dana-Farber Cancer Institute in Boston and Memorial Sloan-Kettering Cancer Center in New York City.

Go here to read the rest:
Mount Sinai researchers discover gene signature that predicts prostate cancer survival

Fibulin-3 Represents a Sensitive and Specific Marker for the Diagnosis of Mesothelioma, Offering a Potential Tool for Early Diagnosis, Monitoring

Newswise NEW YORK, October 11, 2012 Researchers at NYU School of Medicine have discovered the protein product of a little-known gene may one day prove useful in identifying and monitoring the development of mesothelioma in early stages, when aggressive treatment can have an impact on the progression of disease and patient prognosis.

This gene produces a protein, fibulin-3, that is present in levels four to five times higher in the plasma of patients with mesothelioma compared to levels in asbestos-exposed patients or patients with several other conditions that cause tumors in the chest, said lead investigator Harvey I. Pass, MD, the Stephen E. Banner Professor of Thoracic Oncology, vice chair of research for the Department of Cardiothoracic Surgery and division chief of General Thoracic Surgery at NYU Langone Medical Center. We didnt know anything about this proteins role in mesothelioma before this study, but it may be an extremely useful tool for monitoring patients under treatment and possibly even diagnosing the development of mesothelioma at early stages. This marker is as exciting as any biomarker in mesothelioma today and warrants further research and validation by the scientific community.

The study appears in the October 11 issue of the New England Journal of Medicine.

Malignant mesothelioma is a rare but aggressive thoracic cancer that can develop several decades after exposure to asbestos. Diagnosis is often delayed until patients begin to show symptoms, including shortness of breath, cough, chest pain and, in advanced stages, weight loss and night sweats.

Often, patients with mesothelioma seek treatment when the shortness of breath becomes a noticeable problem. At that point, an x-ray typically reveals fluid in the chest, but many doctors fail to inquire about asbestos exposure upon receiving this report. Rather, doctors initially associate fluid in the chest with pneumonia or other inflammatory conditions, further delaying diagnosis, Dr. Pass explained.

Despite advances in chemotherapy, radiation therapy, and surgical management for malignant mesothelioma, the median survival for patients diagnosed with mesothelioma remains 12 months.

There is a great need for something some marker or test that will heighten the alarm that a patient presenting with new onset chest fluid could have mesothelioma, Dr. Pass said. Our findings indicate that a simple blood test may lead physicians to ask questions about asbestos exposure and consider whether the medical history and symptoms are compatible with mesothelioma.

Dr. Pass and his team are dedicated to finding diagnostic biomarkers genes, proteins or other molecules that are not only different in people with mesothelioma compared with cancerfree individuals who have been exposed to asbestos, but also different when compared to individuals with a variety of conditions that could cause fluid in the chest other than mesothelioma.

Fibulin-3 is a protein that floats around outside cells, coating the cells and free floating in blood plasma and extracellular fluid. For the current study, the research team compared levels of fibulin-3 in two separate cohorts of patients who were exposed to asbestos through their jobs: a group of iron workers and other asbestos-exposed individuals in Detroit, and a group of insulators in New York. Both cohorts included individuals who had been exposed to asbestos but did not develop mesothelioma, as well as individuals with a confirmed mesothelioma diagnosis. The researchers found that fibulin-3 expression was markedly elevated in the plasma of the patients with mesothelioma compared with the plasma of patients without mesothelioma. But the researchers wondered if maybe the elevated fibulin-3 levels were associated with other conditions, in addition to mesothelioma, that are associated with the development of chest tumors.

Read the original post:
High Levels of Blood-Based Protein Specific to Mesothelioma

ScienceDaily (Oct. 10, 2012) Researchers from Mount Sinai School of Medicine have identified a six-gene signature that can be used in a test to predict survival in men with aggressive prostate cancer, according to new research published in the October issue of The Lancet Oncology. This is the first study to demonstrate how prognostic markers may be useful in a clinical setting.

Using blood from 202 men with treatment-resistant prostate cancer, researchers found six genes characteristic of treatment-resistant prostate cancer. Men with the six-gene signature were high-risk, with a survival time of 7.8 months, and men without it were low-risk, with a survival time of approximately 34.9 months. A replication study of 140 additional patients validated these findings. William K. Oh, MD, Chief of the Division of Hematology and Medical Oncology of The Tisch Cancer Institute at The Mount Sinai Medical Center, led the research team.

"There is an urgent need for predictive models that help assess how aggressive the disease is in prostate cancer patients, as survival can vary greatly," said Dr. Oh. "Our six-gene model, delivered in a simple blood test, will allow clinicians to better determine the course of action for their patients, determine clinical trial eligibility, and lead to more targeted studies in late-stage disease."

Until now, disease prognosis in advanced prostate cancer could only be determined through clinical predictors or, occasionally, tumor biopsies with only moderately predictive results. This study shows the efficacy of the six-gene model blood test in determining length of survival.

"The genes noted in the model suggest possible changes in the immune system related to late-stage disease that warrant further study as a target for immune-based therapies," said Dr. Oh.

Dr. Oh's team is conducting additional studies exploring the feasibility of the six-gene signature in other types of prostate cancer, the stability of the signature during the course of a patient's illness, and the predictive ability of this signature in patients with prostate cancer treated with immune-based therapies.

This work was done in collaboration with colleagues at Dana-Farber Cancer Institute in Boston and Memorial Sloan-Kettering Cancer Center in New York City.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

Follow this link:
Gene signature predicts prostate cancer survival

WASHINGTON (AP) Too often, newborns die of genetic diseases before doctors even know what is to blame. Now scientists have found a way to decode those babies' DNA in just days instead of weeks, moving gene-mapping closer to routine medical care.

The idea: Combine faster gene-analyzing machinery with new computer software that, at the push of a few buttons, uses a baby's symptoms to zero in on the most suspicious mutations. The hope would be to start treatment earlier, or avoid futile care for lethal illnesses.

Wednesday's study is a tentative first step: Researchers at Children's Mercy Hospital in Kansas City, Missouri, mapped the DNA of just five children, and the study wasn't done in time to help most of them.

But the hospital finds the results promising enough that by year's end, it plans to begin routine gene-mapping in its neonatal intensive care unit - and may offer testing for babies elsewhere, too - while further studies continue, said Dr. Stephen Kingsmore, director of the pediatric genome center at Children's Mercy.

``For the first time, we can actually deliver genome information in time to make a difference,'' predicted Kingsmore, whose team reported the method in the journal Science Translational Medicine. Even if the diagnosis is a lethal disease, ``the family will at least have an answer. They won't have false hope,'' he added.

More than 20 percent of infant deaths are due to a birth defect or genetic diseases, the kind caused by a problem with a single gene. While there are thousands of such diseases - from Tay-Sachs to the lesser known Pompe disease, standard newborn screening tests detect only a few of them. And once a baby shows symptoms, fast diagnosis becomes crucial.

Sequencing whole genomes - all of a person's DNA - can help when it is not clear what gene to suspect. But so far it has been used mainly for research, in part because it takes four to six weeks to complete and is very expensive.

Wednesday, researchers reported that the new process for whole-genome sequencing can take just 50 hours, half that time to perform the decoding from a drop of the baby's blood, and the rest to analyze which of the DNA variations uncovered can explain the child's condition.

That's an estimate: The study counted only the time the blood was being decoded or analyzed, not the days needed to ship the blood to Essex, England, home of a speedy new DNA decoding machine made by Illumina, Inc., or to ship back the results for Children's Mercy's computer program to analyze. Kingsmore said the hospital is awaiting arrival of its own decoder, when 50 hours should become the true start-to-finish time.

Specialists not involved with the study said it signals the long-promised usefulness of gene-mapping to real-world medicine finally is close. ``Genomic sequencing like this is very practical and very real now,'' said Dr. Arthur Beaudet of the Baylor College of Medicine, which also is working to expand genomic testing in children. ``Fast forward a year, and I think this kind of thing will probably be pretty routine.''

View post:
Test Spots Newborn Gene Disease

Featured Article Academic Journal Main Category: Psychology / Psychiatry Also Included In: Obesity / Weight Loss / Fitness;Anxiety / Stress;Genetics Article Date: 10 Oct 2012 - 0:00 PDT

Current ratings for: Rare Gene Deletion Tied To Psychiatric Disease And Obesity

4 (1 votes)

5 (1 votes)

In their paper, Carl Ernst, a professor in the Department of Psychiatry at the Faculty of Medicine of McGill University in Montreal, Quebec, Canada, and colleagues, suggest deletion of BDNF, a nervous system growth factor that is important for brain development, leads to major depression, anxiety and obesity.

They are confident they have found a molecular pathway that plays a key role in psychopathology.

Ernst, who is also a researcher at the Douglas Mental Health University Institute (affiliated to McGill), says scientists have been scouring the genome to find regions in our DNA that may tell us something about the genetic origins of psychiatric disorders.

For some time, thanks to animal studies, it has been proposed that BDNF plays several roles in the brain, but no study has yet shown what happens when it is missing from the genome.

In this study, the participants were 35,000 people referred for genetic screening, and over 30,000 controls, in Canada, Europe and the US.

From the genetic screening, five people (including three children) tested positive for BDNF deletions. All five were obese and had mild to moderate intellectual impairment, plus a mood disorder, which in the children comprised anxiety disorder, aggressive disorder, or attention deficit-hyperactivity disorder (ADHD), and in the older subjects comprised anxiety or major depressive disorder.

View original post here:
Rare Gene Deletion Tied To Psychiatric Disease And Obesity

WASHINGTON (AP) -

Too often, newborns die of genetic diseases before doctors even know what's to blame. Now scientists have found a way to decode those babies' DNA in just days instead of weeks, moving gene-mapping closer to routine medical care.

The idea: Combine faster gene-analyzing machinery with new computer software that, at the push of a few buttons, uses a baby's symptoms to zero in on the most suspicious mutations. The hope would be to start treatment earlier, or avoid futile care for lethal illnesses.

Wednesday's study is a tentative first step: Researchers at Children's Mercy Hospital in Kansas City, Mo., mapped the DNA of just five children, and the study wasn't done in time to help most of them.

But the hospital finds the results promising enough that by year's end, it plans to begin routine gene-mapping in its neonatal intensive care unit - and may offer testing for babies elsewhere, too - while further studies continue, said Dr. Stephen Kingsmore, director of the pediatric genome center at Children's Mercy.

"For the first time, we can actually deliver genome information in time to make a difference," predicted Kingsmore, whose team reported the method in the journal Science Translational Medicine.

Even if the diagnosis is a lethal disease, "the family will at least have an answer. They won't have false hope," he added.

More than 20% of infant deaths are due to a birth defect or genetic diseases, the kind caused by a problem with a single gene. While there are thousands of such diseases - from Tay-Sachs to the lesser known Pompe disease, standard newborn screening tests detect only a few of them. And once a baby shows symptoms, fast diagnosis becomes crucial.

Sequencing whole genomes - all of a person's DNA - can help when it's not clear what gene to suspect. But so far it has been used mainly for research, in part because it takes four to six weeks to complete and is very expensive.

Wednesday, researchers reported that the new process for whole-genome sequencing can take just 50 hours - half that time to perform the decoding from a drop of the baby's blood, and the rest to analyze which of the DNA variations uncovered can explain the child's condition.

Read the rest here:
2-day test can spot gene diseases in newborns

Too often, newborns die of genetic diseases before doctors even know what's to blame. Now scientists have found a way to decode those babies' DNA in just days instead of weeks, moving gene-mapping closer to routine medical care.

The idea: Combine faster gene-analyzing machinery with new computer software that, at the push of a few buttons, uses a baby's symptoms to zero in on the most suspicious mutations. The hope would be to start treatment earlier, or avoid futile care for lethal illnesses.

Wednesday's study is a tentative first step: Researchers at Children's Mercy Hospital in Kansas City, Mo., mapped the DNA of just five children, and the study wasn't done in time to help most of them.

But the hospital finds the results promising enough that by year's end, it plans to begin routine gene-mapping in its neonatal intensive care unit and may offer testing for babies elsewhere, too while further studies continue, said Dr. Stephen Kingsmore, director of the pediatric genome center at Children's Mercy.

Even if the diagnosis is a lethal disease, "the family will at least have an answer. They won't have false hope," said Kingsmore, who team reported the method in the journal Science Translational Medicine.

More than 20 per cent of infant deaths are due to a birth defect or genetic diseases, the kind caused by a problem with a single gene. While there are thousands of such diseases from Tay-Sachs to the lesser known Pompe disease, standard newborn screening tests detect only a few of them. And once a baby shows symptoms, fast diagnosis becomes crucial.

Sequencing whole genomes all of a person's DNA can help when it's not clear what gene to suspect. But so far it has been used mainly for research, in part because it takes four to six weeks to complete and is very expensive.

Wednesday, researchers reported that the new process for whole-genome sequencing can take just 50 hours half that time to perform the decoding from a drop of the baby's blood, and the rest to analyze which of the DNA variations uncovered can explain the child's condition.

That's an estimate: The study counted only the time the blood was being decoded or analyzed, not the days needed to ship the blood to Essex, England, home of a speedy new DNA decoding machine made by Illumina, Inc. or to ship back the results for Children's Mercy's computer program to analyze. Kingsmore said the hospital is awaiting arrival of its own decoder, when 50 hours should become the true start-to-finish time.

Specialists not involved with the study said it signals the long-promised usefulness of gene-mapping to real-world medicine finally is close.

Read the original post:
Gene diseases in newborns spotted with 2-day test

WASHINGTONToo often, newborns die of genetic diseases before doctors even know what's to blame. Now scientists have found a way to decode those babies' DNA in just days instead of weeks, moving gene-mapping closer to routine medical care.

The idea: Combine faster gene-analyzing machinery with new computer software that, at the push of a few buttons, uses a baby's symptoms to zero in on the most suspicious mutations. The hope would be to start treatment earlier, or avoid futile care for lethal illnesses.

Wednesday's study is a tentative first step: Researchers at Children's Mercy Hospital in Kansas City, Mo., mapped the DNA of just five children, and the study wasn't done in time to help most of them.

But the hospital finds the results promising enough that by year's end, it plans to begin routine gene-mapping in its neonatal intensive care unit -- and may offer testing for babies elsewhere, too -- while further studies continue, said Dr. Stephen Kingsmore, director of the pediatric genome center at Children's Mercy.

"For the first time, we can actually deliver genome information in time to make a difference," predicted Kingsmore, whose team reported the method in the journal Science Translational Medicine.

Even if the diagnosis is a lethal disease, "the family will at least have an answer. They won't have false hope," he added.

More than 20 percent of infant deaths are due to a birth defect or genetic diseases, the kind caused by a problem with a single gene. While there are thousands of such diseases -- from Tay-Sachs to the lesser known Pompe disease, standard newborn screening tests detect only a few of them. And once a baby shows symptoms, fast diagnosis becomes crucial.

Sequencing whole genomes - all of a person's DNA - can help when it's not clear what gene to suspect. But so far it has been used mainly for research, in part because it takes four to six weeks to complete and is very expensive.

Wednesday, researchers reported that the new process for whole-genome sequencing can take just 50 hours -- half that time to perform the decoding from a drop of the baby's blood, and the rest to analyze which of the DNA variations uncovered can explain the child's condition.

That's an estimate: The study counted only the time the blood was being decoded or analyzed, not the days needed to ship the blood to Essex, England, home of a speedy new DNA decoding machine made by Illumina, Inc. -- or to ship back the results for Children's Mercy's computer program to analyze. Kingsmore said the hospital is awaiting arrival of its own decoder, when 50 hours should become the true start-to-finish time.

Continue reading here:
Rapid gene-mapping test may diagnose disease in newborns