A new study from researchers at the University of Michigan Rogel Cancer Center finds that the gene FOXA1 overrides normal biology in three different ways to drive prostate cancer. They refer to the three classes as FAST, FURIOUS, and LOUD to reflect their unique features. The findings are published in Nature.
"It's quite intriguing and complex biology," says senior study author Arul M. Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology and S.P. Hicks Endowed Professor of Pathology at Michigan Medicine.
Gene - Oncogene - Ways - Abhijit - Parolia
"We found that the same gene can be turned into an oncogene in three different ways," says Abhijit Parolia, a molecular and cellular pathology graduate student and co-first author on this study. "One moves fast in the nucleus, the second binds to chromatin furiously and the third amplifies itself to be loud. These three alteration classes have different clinical implications for patients."
Class 1 mutations are FAST. They cause the transcription factor to travel more quickly through the DNA, allowing the partnering androgen receptor to activate expression of cancer-promoting genes. Imagine the driver racing forward at high speed. These mutations are seen in early stage prostate cancer and are likely what triggers the disease.
Class - Mutations - FURIOUS - Mutation - Portion
Class 2 mutations are FURIOUS. The mutation causes a portion of the FOXA1 molecule to be cut off. This truncated molecule binds very strongly to the DNA, preventing normal FOXA1 from binding. These mutations are found in lethal hormone-therapy resistant prostate cancer and promote the cancer's spread to distant sites. Think of the mutant as furiously binding DNA and dominantly enabling the cancer's aggressive features.
Class 3 mutations are LOUD. They involve complex...
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