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 (AACR). He said the work was the result of collaboration among University of California, San Francisco (UCSF), the Oregon Health & Science University (OHSU), the University of California at Berkley and the Samsung Advanced Institute of Technology.

Complex changes in TP53
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.

Which mutations lead to precancerous lesions
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.

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

For more information:
Durinck S, Ho C, Wang NJ, Liao W, Jakkula LR, et al. Temporal Dissection of Tumorigenesis in Primary Cancers. Cancer Discovery Published OnlineFirst June 29, 2011; doi: 10.1158/2159-8290.CD-11-0028.

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