Nav: Home

New computer program can help uncover hidden genomic alterations that drive cancers

April 18, 2016

Cancer is rarely the result of a single mutation in a single gene. Rather, tumors arise from the complex interplay between any number of mutually exclusive abnormal changes in the genome, the combinations of which can be unique to each individual patient. To better characterize the functional context of genomic variations in cancer, researchers at University of California San Diego School of Medicine and the Broad Institute developed a new computer algorithm they call REVEALER.

This tool, described in a paper published April 18 in Nature Biotechnology, is designed to help researchers identify groups of genetic variations that together associate with a particular way cancer cells get activated, or how they respond to certain treatments. REVEALER is available for free to the global scientific community via the bioinformatics software portal GenePattern.org .

"This computational analysis method effectively uncovers the functional context of genomic alterations, such as gene mutations, amplifications, or deletions, that drive tumor formation," said senior author Pablo Tamayo, PhD, professor and co-director of the UC San Diego Moores Cancer Center Genomics and Computational Biology Shared Resource.

Tamayo and team tested REVEALER using The Cancer Genome Atlas (TCGA), the National Institutes of Health's database of genomic information from more than 500 human tumors representing many cancer types. REVEALER revealed gene alterations associated with the activation of several cellular processes known to play a role in tumor development and response to certain drugs. Some of these gene mutations were already known, but others were new. For example, the researchers discovered new activating genomic abnormalities for beta-catenin, a cancer-promoting protein, and for the oxidative stress response that some cancers hijack to increase their viability.

REVEALER is a powerful approach but requires as input high-quality genomic data and a significant number of cancer samples, which can be a challenge, Tamayo says. But REVEALER is more sensitive at detecting similarities between different types of genomic features and less dependent on simplifying statistical assumptions, compared to other methods, he says.

"This study demonstrates the potential of combining functional profiling of cells with the characterizations of cancer genomes via next generation sequencing," said co-senior author Jill P. Mesirov, PhD, professor and associate vice chancellor for computational health sciences at UC San Diego School of Medicine.
-end-
Study co-authors include Jong Wook Kim, Joseph Rosenbluh, Yashaswi Shrestha, David J. Konieczkowski, Cory M. Johannessen, Andrew Aguirre, Francisca Vazquez, Eliezer M. Van Allen, Diane D. Shao, David A. Barbie, Broad Institute and Dana-Farber Cancer Institute; Olga B. Botvinnik, Broad Institute and UC San Diego; Omar Abudayyeh, Peter S. Hammerman, Travis I. Zack, Broad Institute, Dana-Barber Cancer Institute and Harvard University; Chet Birger, Daniel DiCara, Arthur Liberzon, Mahmoud Ghandi, Barbara A. Weir, Aviad Tsherniak, Michael Noble, Gad Getz, Jesse S. Boehm, Broad Institute; Mohamed E. Abazeed, Broad Institute and Cleveland Clinic; Amir Reza Alizad-Rahvar, Masoud Ardakani, University of Alberta; Gabriela Alexe, Broad Institute, Dana-Farber Cancer Institute, Boston Children's Hospital and Boston University; Heidi Greulich, Levi A. Garraway, William C. Hahn, Broad Institute, Dana-Farber Cancer Institute and Brigham and Women's Hospital; Rameen Beroukhim, Broad Institute, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard University; Chiara Romualdi, and Gabriele Sales, University of Padova.

This research was funded, in part, by the National Cancer Institute at the National Institutes of Health (grants R01CA154480, R01CA121941, U01CA176058, R01CA109467 and U01CA184898-02).

University of California - San Diego

Related Cancer Articles:

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Space
One of the most consistent questions we get at the show is from parents who want to know which episodes are kid-friendly and which aren't. So today, we're releasing a separate feed, Radiolab for Kids. To kick it off, we're rerunning an all-time favorite episode: Space. In the 60's, space exploration was an American obsession. This hour, we chart the path from romance to increasing cynicism. We begin with Ann Druyan, widow of Carl Sagan, with a story about the Voyager expedition, true love, and a golden record that travels through space. And astrophysicist Neil de Grasse Tyson explains the Coepernican Principle, and just how insignificant we are. Support Radiolab today at Radiolab.org/donate.