News Release

To view the TCGA prostate cancer findings in Cell, click here.

Thursday, November 5, 2015
Noon EST

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TCGA study identifies seven distinct subytypes of prostate cancer

A comprehensive analysis of 333 prostate cancers identified key genetic alterations that may help improve classification and treatment of the disease. While 90 percent of prostate cancers are now identified as clinically localized tumors, once diagnosed, these cancers tend to have a heterogeneous and unpredictable course of progression, ranging from slow-growing to fatal disease. The new analysis, by investigators from The Cancer Genome Atlas (TCGA) Research Network, revealed seven new molecular subtypes of prostate cancer based on known and novel genetic drivers of the disease.  These subtypes may therefore have prognostic and therapeutic implications. Of the seven subtypes, four are characterized by gene fusions (in which parts of two separate genes are linked to form a hybrid gene) involving members of the ETS family of transcription factors (ERG, ETV1, ETV4, and FLI1), and the other three are defined by mutations of the SPOP, FOXA1, and IDH1 genes. Notably, the IDH1 mutation was identified as a driver of prostate cancers that occur at younger ages. Although most (74 percent) of the analyzed tumors could be categorized into one of the seven molecular subtypes, the remaining 26 percent of prostate tumors in this analysis could not be categorized because molecular alterations driving their growth were not identified. Prostate cancer is expected to be diagnosed in over 220,000 men in the U.S. this year and is the fourth most common tumor type worldwide.

Another finding from this analysis was that gene expression profiles differed based on whether the tumors were driven by gene fusions or by mutations. Within the mutation-driven tumors, the SPOP and FOXA1 gene subtypes shared similar patterns of DNA methylation, a chemical modification of DNA that inhibits gene expression; somatic copy-number alteration, or change in the number of copies of a gene in a cell; and messenger RNA expression, which is a measure of gene activity. These genomic commonalities suggest that mutations in SPOP and FOXA1 genes cause similar disruptions in the cell to bring about cancer. Additionally, the SPOP and FOXA1 subtypes showed the highest levels of androgen receptor-mediated gene expression, suggesting potential preventive and therapeutic possibilities targeting androgens, which are male sex hormones that can stimulate the growth of prostate cancer.  The researchers, led by Chris Sander, Ph.D., Memorial Sloan-Kettering Cancer Center, New York, published their results online November 5, 2015, in Cell. TCGA is a collaboration jointly supported and managed by the National Cancer Institute and the National Human Genome Research Institute, both parts of the National Institutes of Health.