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Scientists discover distinct molecular subtype of prostate cancer
Date:5/20/2012

ing of 112 prostate tumors and normal tissue pairs. The findings were verified in another 400 prostate cancer patient samples from other institutions around the country. Dr. Barbieri of Weill Cornell, Dr. Baca and Dr. Michael Lawrence of the Broad Institute are the study's co-lead investigators.

The teams found three genes significantly altered in the prostate cancers, but not in non-cancerous tissue. In addition to SPOP mutations, which occurred in 6 to 15 percent of tumors across multiple independent cohorts, they found mutations in the FOXA1 and MED12 genes, each of which are found in about 4 percent of patient tumors.

Further examination revealed the interesting nature of SPOP mutations. SPOP belongs to a class of proteins known as ubiquitin ligases, whose role is to mark other proteins in the cell for degradation. The mutations the team discovered all occur where the SPOP protein binds to the other proteins it should tag. "That suggests that there might be an accumulation of proteins in the cell that aren't cleaned out and this might lead to cancer growth, or the mutations could be removing proteins that help prevent unchecked cell growth," says Dr. Rubin. "We are working hard to understand what is happening."

Because they were also found in premalignant lesions, the researchers suspect SPOP mutations occur early in development of the cancer. "This could be one of the switches that turns prostate cancer on," Dr. Rubin says.

They also do not yet know if SPOP mutations define a more aggressive type of prostate cancer.

Dr. Rubin further notes that SPOP mutations and TMPRSS2-ERG fusion genes never occur in the same tumor. They are mutually exclusive, implying two distinct molecular classes of prostate cancer.

"These studies really do provide a comprehensive catalog of the genetic changes occurring in prostate cancer," Dr. Rubin says.

As a urologist who treats men with prostate cancer, Dr. Barbieri says
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Contact: Lauren Woods
law2014@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

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