Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Study Finds Rules for Cancer Drivers

Published: Monday, September 30, 2013
Last Updated: Monday, September 30, 2013
Bookmark and Share
Any number of alterations to an individual’s genetic code has the potential to make a cell malfunction and proliferate into cancer tumors.

Identifying the genetic changes that lead to cancer – and the rules that govern those changes – has been a key goal in the field of cancer genomics. It is a task made more challenging by the diversity of cancer types and the seemingly distinct biology of different types of cancers.

This week, researchers from the Genome Characterization Center (GCC) at the Broad Institute announced that they had identified some rules that apply across cancers for a specific type of genetic mutation – somatic copy number alterations (SCNAs). SCNAs are deletions or duplications of certain regions of the genome, and are some of the most common mutations that occur in cancer.

In the largest such study to date, the team looked at nearly 5,000 cancer samples from across 12 cancer types – including breast, bladder, and colon cancer, among others – for patterns in the occurrence of SCNAs. Their study, which appears in Nature Genetics, identified common ways in which these copy number changes are generated in cancer, and located specific genes and regions involved.

“Our goal was to find patterns that are universal across cancer,” said Matthew Meyerson, a senior associate member at the Broad and one of the study’s co-senior authors. “Finding these patterns across cancer types suggests that different cancers tend to result from similar or even the same underlying events, and therefore arise from many of the same pathways.”

The findings also serve as a database that researchers can draw from in future investigations.

“This paper gives researchers a large compendium of new genes and processes to look at that may play an essential role in individual cancers, enabling the research community to identify new causes and molecular pathways that may one day be targeted to treat cancer,” said Rameen Beroukhim, the lead investigator of the study and a co-senior author of the paper. Beroukhim is an associate member of the Broad, and an assistant professor at Dana-Farber Cancer Institute and Harvard Medical School.

The team found that, across cancer types, somatic copy number alterations adhered to the following rules:

Whole-genome doubling is associated with higher rates of every other type of copy number alteration. Whole-genome doubling is one of the major sources of copy number changes in tumors, occurring in about 37% of cancers. As the term suggests, it happens when the entire genome of an organism duplicates, so instead of producing the usual two of each chromosome, a person will produce four. The GCC study found that, in cancer, whole-genome doubling tends to trigger additional copy number alterations. The team found that the genes TP53 and CCNE1 – which had previously been linked to whole-genome doubling – were associated with these cancer-related events. They also found two new genes whose mutations contribute to the doubling of cancer genomes: PPP2R2A and PPP2R1A.

SCNAs that occur within chromosomes and those that occur at the ends of chromosomes are most likely caused by different mechanisms. The team found that copy number alterations that begin at the protective ends of chromosomes (called “telomeres”) tend to be longer than alterations that occur within chromosomes. The significant difference between these two types of SCNAs suggests that two distinct mechanisms are at work: one that causes copy number alterations that extend at the telomere, and a different one that can create internal, chromosomal copy number changes.

There are 140 regions of the genome that seem to be affected by somatic copy number alterations. Across all 12 cancer types examined in the study, these 140 regions were consistently altered. Of these regions, only 35 contained genes that were previously linked to cancer. The remaining regions house a large number of new candidate genes that may prove to be cancer drivers.

SCNAs can affect the epigenetic regulators that control how genes are expressed, contributing to cancer. Many of the 140 regions identified by the study are known to contain epigenetic regulators. These regulators modify how DNA is folded within the cell and what parts of the DNA’s genetic code can be read, which in turn affects how genes are expressed. This evidence suggests that some cancer patient populations may benefit from treatments that target these epigenetic regulators.

The GCC study was conducted as part The Cancer Genome Atlas (TCGA) Project, a national, multi-institution collaboration to characterize the genomes of over 20 types of cancer and to uncover the molecular basis of the disease. The Broad GCC site is one of six TCGA Genome Characterization Centers. Meyerson, who is one of the Broad GCC’s principal investigators, said the goal of the center is to provide copy number analysis of all of the tumors that are analyzed by TCGA.

“This paper is really the first report of that copy number analysis, systematically across cancer,” explained Meyerson, who is also an associate professor of pathology and medical oncology at Dana-Farber Cancer Institute. “It is the culmination of years of work in this area at the Broad, and the product of a data generation and analytical pipeline that is built upon a very long tradition of Broad research.”

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More Than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Screen of Human Genome Reveals Set of Genes Essential for Cellular Viability
Using two complementary analytical approaches, scientists at Whitehead Institute and Broad Institute of MIT and Harvard have for the first time identified the universe of genes in the human genome essential for the survival and proliferation of human cell lines or cultured human cells.
Monday, October 19, 2015
DARPA Awards $32 Million Contract to MIT, Broad Institute Foundry
A facility at the Broad Institute of MIT and Harvard and MIT that aims to achieve the full potential of engineering biology has received a five-year, $32 million contract from the Defense Advanced Research Projects Agency (DARPA).
Monday, September 28, 2015
Diagnostics Breakthrough Brings Viral Sequencing to Doctors’ Toolkit
New screening tool produces up to 10,000-fold improvement in viral matches compared with traditional high-throughput methods.
Monday, September 28, 2015
Scientists Discover New System For Human Genome Editing
CRISPR-Cpf1 system could disrupt both scientific and commercial landscape.
Monday, September 28, 2015
Researchers Develop a New Means of Killing Harmful Bacteria
Engineered particles are capable of producing toxins that are deadly to targeted bacteria.
Friday, June 26, 2015
Broad Institute & Google Genomics Combine Bioinformatics and Computing Expertise
Both companies explore how to break down major technical barriers that increasingly hinder biomedical research.
Thursday, June 25, 2015
CRISP-Disp Leverages CRISPR-Cas9 to Deliver RNA Structures to Targets in the Genome
A team of researchers from the Broad Institute and the Harvard Stem Cell Institute has developed CRISP-Disp, a method that expands on the CRISPR-Cas9 system, allowing researchers to display multiple, large RNA structures on the Cas9 protein.
Wednesday, June 10, 2015
GTEx: Useful Expression For Cancer Research
GTEx Project has recently published several papers reporting on findings from its two-year pilot phase.
Tuesday, May 26, 2015
Single-cell Analysis Hits its Stride
Advances in technology and computational analysis enable scale and affordability, paving the way for translational studies.
Saturday, May 23, 2015
Highly Efficient New Cas9 for In Vivo Genome Editing
New finding is expected to expand therapeutic and experimental applications of CRISPR.
Tuesday, April 07, 2015
Broad Institute of MIT and Harvard and Bayer Healthcare Expand their Partnership
Collaboration to develop therapies for cardiovascular disease.
Thursday, April 02, 2015
In vivo CRISPR-Cas9 Screen Sheds Light On Cancer Metastasis And Tumor Evolution
Genome-scale study points to drivers of tumor evolution and metastasis, provides roadmap for future in vivo Cas9 screens.
Friday, March 06, 2015
Scientists Map the Human Loop-ome, Revealing a New Form of Genetic Regulation
Researchers describe the results of a five-year effort to map, in unprecedented detail, how the 2-meter long human genome folds inside the nucleus of a cell.
Tuesday, December 23, 2014
Disorder in Gene-Control System is a Defining Characteristic of Cancer, Study Finds
Findings indicate that the disarray in the on-off mechanism is one of the defining characteristics of cancer.
Tuesday, December 23, 2014
Two Studies Identify A Detectable, Pre-Cancerous State In The Blood
Findings pave way for new lines of cancer research focused on detection and prevention.
Thursday, November 27, 2014
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
Kitchen Utensils Can Spread Bacteria Between Foods
In a recent study researchers found that produce that contained bacteria would contaminate other produce items through the continued use of knives or graters—the bacteria would latch on to the utensils commonly found in consumers' homes and spread to the next item.
Exploring the Causes of Cancer
Queen's research to understand the regulation of a cell surface protein involved in cancer.
Safer, Faster Way To Remove Pollutants From Water
Using nanoparticles filled with enzymes proves more effective than current methods.
Drug May Prevent Life-Threatening Muscle Loss in Advanced Cancers
New data describes how an experimental drug can stop life-threatening muscle wasting (cachexia) associated with advanced cancers and restore muscle health.
Ancient Viral Molecules Essential for Human Development
Genetic material from ancient viral infections is critical to human development, according to researchers at the Stanford University School of Medicine.
Novel Tumor Treatment
In the first published results from a $386,000 National Cancer Institute grant awarded earlier this year, a paper by Scott Verbridge and Rafael Davalos has been published.
Speeding Up the Process of Making Vaccines
System uses a freeze-dry concept to develop "just-add-water" solution.
Chemical Design Made Easier
Rice University scientists prepare elusive organocatalysts for drug and fine chemical synthesis.
New Analysis Technique for Chiral Activity in Molecules
Professor Hyunwoo Kim of the Chemistry Department and his research team have developed a technique that can easily analyze the optical activity of charged compounds by using nuclear magnetic resonance (NMR) spectroscopy.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos