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."
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.
Bill Schaller | EurekAlert!
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
29.03.2017 | Health and Medicine
29.03.2017 | Earth Sciences
29.03.2017 | Trade Fair News