title: Uncovering the genetic landscape driving castration-resistant prostate cancer.
abstract: Identification of the mechanisms that drive progression of metastatic castration-resistant prostate cancer (CRPC) has fostered interest since early androgen studies in the 1940s. Little knowledge has surfaced about the role mutations play in prostate cancer development. A group at the Michigan Center for Translation Pathology studied exomes of lethal, metastatic CRPC and documented the overall mutation rates. In classifying these mutations, the monoclonal cause of CRPC was recognized. Nine identified genes showed significant mutations. Six of these genes had previously been reported as mutated in prostate cancer. The analysis also found significantly mutated androgen receptor (AR) cofactors and linked proteins, including FOXA1 and MLL2. Another finding concerned an aberration in CHD1. Prostate cancers with deletions or mutations in CHD1 showed a strong correlation with ETS gene family fusion negative prostate cancers (96%). In profiling these exomes, this group provides an original method to identify deletions and mutations that drive CRPC progression.
authors.affiliation: Clinical Pharmacology Program, Medical Oncology Branch, Office of the Clinical Director, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Martin
authors.forename: Cody J
authors.initials: CJ
authors.lastname: Peer
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
mesh_terms: D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics*
keywords: castration-resistant prostate cancer; genetics; mutations
references.citation: Carcinogenesis. 2012 Mar;33(3):572-80
references.pmid: 22232738
references.citation: EMBO J. 2010 Jul 7;29(13):2147-60
references.pmid: 20517297
references.citation: Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):17087-92
references.pmid: 21949389
references.citation: Nature. 2012 Jul 12;487(7406):239-43
references.pmid: 22722839
references.citation: JAMA. 2005 Jul 13;294(2):238-44
references.pmid: 16014598
references.citation: Cancer Cell. 2011 Jun 14;19(6):792-804
references.pmid: 21620777
references.citation: Genes Dev. 2010 Sep 15;24(18):1967-2000
references.pmid: 20844012
references.citation: Cancer Res. 2011 Nov 1;71(21):6738-6748
references.pmid: 21900400
references.citation: Nature. 2011 Jul 27;476(7360):298-303
references.pmid: 21796119
references.citation: Mol Cancer. 2012 Aug 06;11:52
references.pmid: 22867098