(Press-News.org) BOSTON—Scanning the DNA of nearly 5,000 tumor samples, a team led by scientists at Dana-Farber Cancer Institute and the Broad Institute has identified 140 regions of scrambled genetic code believed to contain many undiscovered cancer genes.
The researchers said the mapping of the abnormal regions gives cancer scientists a starting point from which to search for as-yet undiscovered oncogenes and broken tumor-suppressor genes, which allow cells to divide and grow uncontrollably. Published in the October issue of Nature Genetics, the results are part of an ongoing international research effort to define the landscape of DNA mutations and other genetic changes that fuel the development of cancer.
The authors said it is the largest analysis to date of the role of DNA "copy number alterations" across several types of cancer. Normal cells carry two copies of the 20,000 genes that make up the genome. The genomes of cancer cells typically are riddled with areas where genetic sequences are duplicated or deleted; in fact, copy number alterations affect more of the genome than any other DNA abnormality in cancer. The study's goal was to identify patterns of copy number alterations and determine how they promote cancer.
In the survey of 4,934 cancers of 11 types, "we found that cancers often undergo doubling of the entire genomes, followed by large numbers of smaller copy number alteration events," said Rameen Beroukhim, MD, PhD, assistant professor of Medicine at Dana-Farber and an associate member of the Broad Institute. "We also saw a propensity of copy number changes to occur at telomeres [the tips of chromosomes] and they exhibit features indicating they arise from different mechanisms than copy number changes of regions within chromosomes."
Beroukhim is co-senior author of the report along with Matthew Meyerson, MD, PhD, of Dana-Farber and the Broad, and Gad Getz, PhD, of Massachusetts General Hospital and the Broad.
The analysis also revealed 70 regions of the cancer genome that undergo duplications –also known as amplifications – more often than would be expected by chance and 70 regions that contain deletions more often than would be expected by chance. "We expect these 140 regions to contain a number of as-yet unknown oncogenes and tumor suppressor genes," Beroukhim said.
On average, these 140 regions included three to four genes. However, only 35 of the regions contained known oncogenes or tumor suppressor genes previously linked to cancer. "So there is a lot left to discover in the cancer genome," Beroukhim said. "These regions provide the research community a starting point to evaluate possible novel oncogenes and tumor suppressor genes." The results have been made available in a publicly accessible website, http://www.broadinstitute.org/tcga.
He added that further study of the copy number variation database generated by the researchers "will help us understand better how cancers arise and what are the genes involved. And when we understand that, we can develop diagnostics and therapeutics that counteract those genes."
INFORMATION:
The research used data compiled through The Cancer Genome Atlas Pan-Cancer Initiative, part of The Cancer Genome Atlas Project led by the National Cancer Institute and the National Human Genome Research Institute.
Co-first authors of the report are Travis Zack and Steven Schumacher in the Beroukhim lab at Dana-Farber.
The research was funded in part from grants from the National Institutes of Health (U24CA143867, U24CA143845, U54CA143798, U54HG003067, and U24CA143882), the V Foundation, and the Pediatric Low-Grade Astrocytoma Foundation.
—Written by Richard Saltus
About Dana-Farber Cancer Institute
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center, designated a comprehensive cancer center by the National Cancer Institute. It provides adult cancer care with Brigham and Women's Hospital as Dana-Farber/Brigham and Women's Cancer Center and it provides pediatric care with Boston Children's Hospital as Dana-Farber/Boston Children's Cancer and Blood Disorders Center. Dana-Farber is the top ranked cancer center in New England, according to U.S. News & World Report, and one of the largest recipients among independent hospitals of National Cancer Institute and National Institutes of Health grant funding. Follow Dana-Farber on Facebook and on Twitter.
New survey of DNA alterations could aid search for cancer genes
2013-09-27
ELSE PRESS RELEASES FROM THIS DATE:
New species of fascinating opportunistic shelter using leaf beetles
2013-09-27
Many animals construct homes or shelters to escape from biological and physical hostilities. Birds, spiders, termites, ants, bees and wasps are the most famous animal architects. As shelter construction requires considerable investment of resources and time, builders tend to minimize the cost of building while maximizing the benefits.
Builders are rather uncommon among adult leaf beetles though young ones of certain species use own feces to construct a defensive shield. Two closely related, hitherto unknown species of tiny southern Indian leaf beetles, only slightly larger ...
Understanding how infants acquire new words across cultures
2013-09-27
EVANSTON, Ill. --- Infants show strong universals as they acquire their native language, but a recent study with infants acquiring Korean also reveals that there are striking language differences.
Sandra Waxman, Louis W. Menk Professor of Psychology at Northwestern University, is senior author of a new study providing the first ever evidence comparing how infants (monolingual, from Korea) acquiring Korean learn new nouns and verbs.
Researchers have long suggested that in "noun friendly" languages including English, infants' attention is focused primarily on objects, ...
Mouse studies reveal promising vitamin D-based treatment for MS
2013-09-27
MADISON -- A diagnosis of multiple sclerosis (MS) is a hard lot. Patients typically get the diagnosis around age 30 after experiencing a series of neurological problems such as blurry vision, wobbly gait or a numb foot. From there, this neurodegenerative disease follows an unforgiving course.
Many people with MS start using some kind of mobility aid -- cane, walker, scooter or wheelchair -- by 45 or 50, and those with the most severe cases are typically bed-bound by 60. The medications that are currently available don't do much to slow the relentless march of the disease. ...
New research helps fight against motor neurone disease
2013-09-27
New research from the University of Sheffield could offer solutions into slowing down the progression of motor neurone disease (MND).
Scientists from the University of Sheffield's Institute for Translational Neuroscience (SITraN) conducted pioneering research assessing how the devastating debilitating disease affects individual patients.
MND is an incurable disease destroying the body's cells which control movement causing progressive disability. Present treatment options for those with MND only have a modest effect in improving the patient's quality of life.
Professor ...
Bright, laser-based lighting devices
2013-09-27
WASHINGTON D.C. Sept. 27, 2013 -- As a modern culture, we crave artificial white lights -- the brighter the better, and ideally using less energy than ever before. To meet the ever-escalating demand for more lighting in more places and to improve the bulbs used in sports stadiums, car headlights and street lamps, scientists are scrambling to create better light-emitting diodes (LEDs) -- solid state lighting devices that are more energy efficient than conventional incandescent or fluorescent light sources.
Just one thing stands in the way: "droop," the term for a scientific ...
3-D models of electrical streamers
2013-09-27
WASHINGTON D.C. September 27, 2013 -- Streamers may be great for decorating a child's party, but in dielectrics, they are the primary origin of electric breakdown. They can cause catastrophic damage to electrical equipment, harm the surrounding environment, and lead to large-scale power outages.
Understanding streamers and the mechanisms behind their initiation, acceleration and branching is necessary to devise better solutions to avoid them. As recently reported in the Journal of Applied Physics, a team of researchers at MIT have developed an accurate 3-D model of streamer ...
A new paradigm for nanoscale resolution MRI has been experimentally achieved
2013-09-27
A team from the University of Illinois at Urbana-Champaign and Northwestern University has devised a novel nuclear magnetic resonance imaging (MRI) technique that delivers a roughly 10¬nanometer spatial resolution. This represents a significant advance in MRI sensitivity -- modern MRI techniques commonly used in medical imaging yield spatial resolutions on the millimeter length scale, with the highest-resolution experimental instruments giving spatial resolution of a few micrometers.
"This is a very promising experimental result," said U. of I. physicist Raffi Budakian, ...
Folic acid deficiency has multigenerational effects
2013-09-27
Researchers from the universities of Calgary and Cambridge, UK, have discovered that a mutation in a gene necessary for the metabolism of folic acid not only impacts immediate offspring but can also have detrimental health effects, such as spina bifida and heart abnormalities, on subsequent generations. The animal study, published this week in the journal Cell, also sheds light on the molecular mechanism of folic acid (also known as folate) during development.
About one in 1,200 children are born with spina bifida. The detrimental effects of folic acid deficiency during ...
Joslin identifies immune cells that promote growth of beta cells in type 1 diabetes
2013-09-27
BOSTON - (September 27, 2013) - Joslin researchers have identified immune cells that promote growth of beta cells in type 1 diabetes. This study provides further evidence of a changed role for immune cells in type 1 diabetes pathology. The study appears online today and will also appear in the January issue of Diabetes.
In type 1 diabetes, the immune system infiltrates pancreatic islets and destroys insulin-producing beta cells. However, previous studies in non-obese diabetic (NOD) mice have suggested that immune cells can also contribute to preserving beta cells. This ...
Study: New medical device extremely effective at preventing HIV in women
2013-09-27
It's often said that the HIV/AIDS epidemic has a woman's face. The proportion of women infected with HIV has been on the rise for a decade; in sub-Saharan Africa, women constitute 60 percent of people living with disease. While preventative drugs exist, they have often proven ineffective, especially in light of financial and cultural barriers in developing nations.
A new intravaginal ring filled with an anti-retroviral drug could help. Developed with support from the National Institute of Allergy and Infectious Diseases by Northwestern University visiting associate professor ...