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This current study looked at different drivers of cancer, which aremutations in specific genes. It focused on the 1-2 percent of DNAin the genome that codes for proteins, and, as such, is one of thelargest "whole exome" sequencing studies published on prostatecancer to date, according to Dr. Garraway. The impetus to search for genes in this way came about because ofthe observation that SPOP appeared to be mutated in some cases ofprostate cancer, says Dr. Christopher Barbieri, a fifth yearurology resident at Weill Cornell who spent a research year in Dr.Rubin's laboratory in the Department of Pathology and LaboratoryMedicine. Broad Institute researchers, led by Dr. Garraway and Dr. SylvanBaca, completed an intensive exome sequencing of 112 prostatetumors and normal tissue pairs. The findings were verified inanother 400 prostate cancer patient samples from other institutionsaround the country. Dr. Barbieri of Weill Cornell, Dr. Baca and Dr.Michael Lawrence of the Broad Institute are the study's co-leadinvestigators. The teams found three genes significantly altered in the prostatecancers, but not in non-cancerous tissue. In addition to SPOPmutations, which occurred in 6 to 15 percent of tumors acrossmultiple independent cohorts, they found mutations in the FOXA1 andMED12 genes, each of which are found in about 4 percent of patienttumors. Further examination revealed the interesting nature of SPOPmutations. SPOP belongs to a class of proteins known as ubiquitinligases, whose role is to mark other proteins in the cell fordegradation. The mutations the team discovered all occur where theSPOP protein binds to the other proteins it should tag. "Thatsuggests that there might be an accumulation of proteins in thecell that aren't cleaned out and this might lead to cancer growth,or the mutations could be removing proteins that help preventunchecked cell growth," says Dr. Rubin. "We are working hard tounderstand what is happening." Because they were also found in premalignant lesions, theresearchers suspect SPOP mutations occur early in development ofthe cancer. "This could be one of the switches that turns prostatecancer on," Dr. Rubin says. They also do not yet know if SPOP mutations define a moreaggressive type of prostate cancer. Dr. Rubin further notes that SPOP mutations and TMPRSS2-ERG fusiongenes 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 thegenetic changes occurring in prostate cancer," Dr. Rubin says. As a urologist who treats men with prostate cancer, Dr. Barbierisays the finding of a SPOP mutation may be one of the breakthroughsoncologists have been seeking. "We have very limited informationavailable to us now on the particular biology of the tumor thatprostate cancer patients have, and how best to treat that cancer,"he says. "But given the finding that SPOP mutations form a distinctkind of cancer, and if you low ball the incidence at about 10percent of all tumors, that means, every year, 25,000 men in theU.S. will be diagnosed with tumors that have this mutation. That isa large number. Knowing what these mutations mean may give us hugeclues about how the patient's cancer will progress and how theymight be best treated in the future," Dr. Barbieri says. "This prostate cancer subtype appears to contain abnormalities incellular processes that are quite new to prostate cancerresearchers, and should open up many future avenues for enhancedunderstanding of the disease," says Dr. Garraway. He adds, "ourcollaboration with the Rubin lab has been crucial to the success ofthis effort. Our groups bring nicely complementary expertise indisease biology, genomics and pathology." "Going forward, we will attempt to define the specific biologicalroles of several new prostate cancer genes, and we willcharacterize new prostate cancer genomic alterations that areemerging through ongoing discovery efforts," Dr. Garraway says. Additional References Citations. I am an expert from goodhlx.com, while we provides the quality product, such as LED Alcohol Tester , China Novelty Wireless Mouse, LED Alcohol Tester,and more.
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