OHSU

Scientists Develop Method to Determine Order of Mutations That Lead to Cancer

06/29/11  Portland, Ore.

Discovery underscores how understanding the abnormalities that develop in the beginning stages of cancer can identify the root causes of the disease

Zeroing in on the early cell mutations that enable a cancer to grow is one of the best ways to find a personalized therapy to stop it. Scientists were able to use a statistical approach for the first time to map out the order in which these abnormalities form to analyze the pattern of DNA changes in advanced skin and ovarian tumors.

The study’s findings, which are published in the July edition of Cancer Discovery, are the result of a collaboration of scientists at the Oregon Health & Science University Knight Cancer Institute; the Lawrence Berkeley National Laboratory, the University of California, San Francisco; and the Samsung Advanced Institute of Technology.

The researchers focused on assessing mutations involving TP53, a gene that normally prevents cells from becoming cancerous. By examining how additional copies of the mutant gene accumulated, they found that changes in TP53 occurred earlier in the disease’s progression than previously believed.

Cancers are the result of multiple mutations, but the ones that happen first set the stage for additional abnormalities.

“We anticipate that this information will enhance our ability to detect cancer early when it is more likely to respond well to treatment,” said Joe Gray, Ph.D., associate director for translational research for the OHSU Knight Cancer Institute.

Early mutations are also important because they are found in every cell of the cancer. “By understanding what happens early in a tumor’s growth, you can develop therapies that will target all cancer cells,” said Paul Spellman, Ph.D., of the Lawrence Berkeley National Laboratory and one of the lead scientists on the study. Spellman will join the OHSU Knight Cancer Institute in July.

Getting information about the order in which aberrations occur previously was difficult because it required the ability to analyze tumors as they developed. But, many cancers aren’t detected until they’ve progressed beyond the initial growth phase. The researchers got around this problem by developing a novel statistical strategy. They integrated measurements of mutations with measurements of structural variations in a genome, which result in the cell having abnormal numbers of copies of one or more sections of DNA. “Now we have an ordering tool that should be broadly useful,” Gray said.

So far, the researchers have investigated only a few types of cancer. Going forward, the analysis could be applied to all cancers. One near-term goal, Gray said, is to identify early mutations for which there are therapies already available.

The research was supported by Stand Up To Cancer and grants from the National Institutes of Health, and the U.S. Department of Defense.

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Particulars

Joe W. Gray, Ph.D., is the Gordon Moore Professor and Chair, Biomedical Engineering Director, OHSU Center for Spatial Systems Biomedicine; Associate Director for Translational Research, OHSU Knight Cancer Institute; Emeritus Professor, University of California San Francisco; and visiting faculty, Lawrence Berkeley National Laboratory.

About the OHSU Knight Cancer Institute

With the latest treatments, technologies, hundreds of research studies and approximately 400 clinical trials, the OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle— an honor earned only by the nation's top cancer centers. The honor is shared among the more than 650 doctors, nurses, scientists and staff who work together at the OHSU Knight Cancer Institute to reduce the impact of cancer. Visit www.ohsuhealth.com/cancer or www.facebook.com/OHSUKnight.

About AACR

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, the AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes 33,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 90 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants, research fellowships and career development awards. The AACR Annual Meeting attracts more than 18,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. Including Cancer Discovery, the AACR publishes seven major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; and Cancer Prevention Research. AACR journals represented 20 percent of the market share of total citations in 2009. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. Follow the AACR on Twitter: @aacr or follow the AACR on Facebook: http://www.facebook.com/aacr.org.

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