Distinct molecular subtype of prostate cancer discovered

A collaborative expedition into the deep genetics of prostate cancer has uncovered a distinct subtype of the disease, one that appears to account for up to 15 percent of all cases, say researchers at Weill Cornell Medical College, the Broad Institute of MIT and Harvard and the Dana-Farber Cancer Institute. In the study, published online May 20 by the journal Nature Genetics, investigators describe how they discovered novel mutations in the SPOP ("S-pop") gene in numerous patient tumors, saying this alteration is thus far unique to prostate cancer and so represents a distinct molecular class that might assist in cancer diagnosis and treatment. Researchers suspect the mutations alter the way cells tag proteins for degradation, leading to an accumulation of dangerous molecules that drive the growth of cancer, perhaps from the beginning. This finding adds to a string of discovery of other genes linked to prostate cancer over the years by this team of investigators, the totality of which is painting a comprehensive picture of how genetic alterations contribute to prostate cancer - the most common cancer in men aside from skin cancer, accounting for the second leading cause of cancer deaths. "These studies constitute a unique, meticulous and intensive look at prostate cancer to see the mechanisms driving this disease," says Dr. Mark A. Rubin, The Homer T. Hirst Professor of Oncology in Pathology and vice chair for experimental pathology at Weill Cornell Medical College. "This study, and our prior findings, tells us that prostate cancer is not just one disease. So far, we have found two main pathways for prostate cancer to develop and this opens the door to development of specialized diagnostic tools and treatments." Mutations in SPOP constitute one major pathway, accounting for up to 15 percent of prostate cancer cases. The other is the 50 percent of prostate cancers containing the so-called "ETS" fusion genes, such as TMPRSS2-ERG. "While there is still a need for increased discovery, it does appear that the overall genetic landscape of prostate cancer is taking shape, and better understanding of the biology and possible therapeutic avenues linked to these alterations has become a very high priority," says Dr. Levi Garraway, a senior associate member of the Broad Institute of MIT and Harvard, and assistant professor at the Dan-Farber Cancer Institute and Harvard Medical School. Dr. Rubin and Dr. Garraway are co-senior investigators for this study and for others that have preceded it in this unique examination of prostate cancer genes. In February 2011, the collaborative groups published a study in Nature in which they used whole genome sequencing to discern global changes and patterns of abnormality in seven prostate tumors and compared them to normal tissue samples. They found that areas of the genome had been unexpectedly rearranged -- just as Dr. Rubin and his collaborators at the University of Michigan had in 2005 with the discovery of the common recurrent TMPRSS2-ERG gene rearrangement, created by the fusion of two different genes.