Scientists Identify Order of Mutations that Lead to Cancer

Scientists have begun to reveal the order of the genetic aberrations in individual cancers in a finding they say is key to early diagnosis and personalized medicine.

“We know that each cancer is a collection of genetic malfunctions,” said Raymond Cho, Ph.D., an assistant clinical professor in the department of dermatology at the University of California, San Francisco (UCSF). “We now show it is possible to determine which changes happen earlier and which ones happen further down the road, even in a single cancer.”

Cho and colleagues reported the findings in Cancer Discovery, the newest journal of the American Association for Cancer Research. He said the work was the result of collaboration among UCSF, the Oregon Health & Science University, the University of California at Berkley and the Samsung Advanced Institute of Technology.

The researchers focused on TP53, a known oncogene present in cutaneous squamous cell carcinomas and serous ovarian adenocarcinomas. By examining how additional copies of the mutant oncogene accumulated, they found that complex changes in TP53 occurred earlier in most cases, rather than later, as had been previously believed.

According to the study, the ability to identify the actual sequence of mutations will help scientists to determine which mutations lead to precancerous lesions and which produce invasive carcinomas.

“Although cancers carry many mutations, the ones that always happen earliest set the stage for additional abnormalities,” said Cho.

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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.