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Cell, 2015-11, Vol.163 (4), p.1011-1025
2015
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Autor(en) / Beteiligte
Titel
The Molecular Taxonomy of Primary Prostate Cancer
Ist Teil von
  • Cell, 2015-11, Vol.163 (4), p.1011-1025
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2015
Quelle
MEDLINE
Beschreibungen/Notizen
  • There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects. [Display omitted] •Comprehensive molecular analysis of 333 primary prostate carcinomas•Seven subtypes defined by ETS fusions or mutations in SPOP, FOXA1, and IDH1•Substantial epigenetic heterogeneity, including a hypermethylated IDH1 mutant subset•Presumed actionable lesions in the PI3K, MAPK, and DNA repair pathways Molecular analysis of 333 primary prostate carcinomas reveals substantial heterogeneity and major subtypes among patients, as well as potentially actionable lesions valuable for clinical management of the disease.

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