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.