A rare variant in EZH2 is associated with prostate cancer risk.

摘要: Prostate cancer (PrCa) is highly heritable, and although rare variants contribute significantly to PrCa risk, few have been identified date. Herein, whole-genome sequencing was performed in a large family featuring multiple affected relatives spanning several generations. A rare, predicted splice site EZH2 variant, rs78589034 (G > A), as segregating with disease all but two individuals the family, one of whom lymphoma bowel female relative. This variant associated risk combined familial and sporadic datasets (n = 1551; odds ratio [OR] 3.55, P 1.20 × 10−5 ). Transcriptome analysis on prostate tumour needle biopsies available for carriers wild-type cases. Although no allele-dependent differences were detected transcripts, distinct differential gene expression signature observed when comparing tissue from the carriers with samples. The expression signature comprised known downstream targets included top-ranked genes, DUSP1, FOS, JUNB and EGR1, which subsequently validated by qPCR. These data provide evidence that rs78589034 increased Tasmanian men further, that this may be perturbed function tissue. Disrupted driver tumourigenesis cancers, including prostate, significant interest therapeutic target.