New survey of DNA alterations could aid search for cancer genes

September 27, 2013 by Richard Saltus

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 and broken , 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 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 that make up the genome. The genomes of 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."

Explore further: 'CYCLOPS' genes may serve as an Achilles' heel in tumor cells

More information: Zack, T et. al. "Pan-cancer patterns of somatic copy number alteration." Nature Genetics DOI: 10.1038/ng.2760

Related Stories

'CYCLOPS' genes may serve as an Achilles' heel in tumor cells

August 15, 2012
BOSTON--The genomic tumult within tumor cells has provided scientists at Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard with clues to an entirely new class of genes that may serve as an Achilles' ...

Genomic sequencing identifies mutant 'drivers' of common brain tumor

January 22, 2013
Large-scale genomic sequencing has revealed two DNA mutations that appear to drive about 15 percent of brain tumors known as meningiomas, a finding that could lead to the first effective drug treatments for the tumors, report ...

Major cancer genotyping study logs 5,000th tumor profile

September 12, 2013
More than 5,000 genetic profiles of tumor DNA have been completed in a large research study by scientists at Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Boston Children's Hospital designed to speed the ...

Scientists find mutation driving pediatric brain tumors

April 30, 2013
A type of low-grade but sometimes lethal brain tumor in children has been found in many cases to contain an unusual mutation that may help to classify, diagnose and guide the treatment of the tumors, report scientists at ...

Pan-cancer studies find common patterns shared by different tumor types

September 26, 2013
Cancer encompasses a complex group of diseases traditionally defined by where in the body it originates, as in lung cancer or colon cancer. This framework for studying and treating cancer has made sense for generations, but ...

Periodic bursts of genetic mutations drive prostate cancer

April 25, 2013
Cancer is typically thought to develop after genes gradually mutate over time, finally overwhelming the ability of a cell to control growth. But a new closer look at genomes in prostate cancer by an international team of ...

Recommended for you

Genetic variants found to play key role in human immune system

August 16, 2017
It is widely recognized that people respond differently to infections. This can partially be explained by genetics, shows a new study published today in Nature Communications by an international collaboration of researchers ...

Active non-coding DNA might help pinpoint genetic risk for psychiatric disorders

August 16, 2017
Northwestern Medicine scientists have demonstrated a new method of analyzing non-coding regions of DNA in neurons, which may help to pinpoint which genetic variants are most important to the development of schizophrenia and ...

Evolved masculine and feminine behaviors can be inherited from social environment

August 15, 2017
The different ways men and women behave, passed down from generation to generation, can be inherited from our social environment - not just from genes, experts have suggested.

Attitudes on human genome editing vary, but all agree conversation is necessary

August 10, 2017
In early August 2017, an international team of scientists announced they had successfully edited the DNA of human embryos. As people process the political, moral and regulatory issues of the technology—which nudges us closer ...

Two genes help older brain gain new cells

August 10, 2017
Two genes act as molecular midwives to the birth of neurons in adult mammals and when inactivated in mice cause symptoms of Fragile X Syndrome, a major cause of mental retardation, a new Yale University study has shown.

New technique searches 'dark genome' for disease mutations

August 10, 2017
When doctors can't find a diagnosis for patient's disease, they turn to genetic detectives. Equipped with genomic sequencing technologies available for less than 10 years, these sleuths now routinely search through a patient's ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.