HES5 silencing is an early and recurrent change in prostate tumourigenesis.

Abstract:

:Prostate cancer is the most common cancer in men, resulting in over 10 000 deaths/year in the UK. Sequencing and copy number analysis of primary tumours has revealed heterogeneity within tumours and an absence of recurrent founder mutations, consistent with non-genetic disease initiating events. Using methylation profiling in a series of multi-focal prostate tumours, we identify promoter methylation of the transcription factor HES5 as an early event in prostate tumourigenesis. We confirm that this epigenetic alteration occurs in 86-97% of cases in two independent prostate cancer cohorts (n=49 and n=39 tumour-normal pairs). Treatment of prostate cancer cells with the demethylating agent 5-aza-2'-deoxycytidine increased HES5 expression and downregulated its transcriptional target HES6, consistent with functional silencing of the HES5 gene in prostate cancer. Finally, we identify and test a transcriptional module involving the AR, ERG, HES1 and HES6 and propose a model for the impact of HES5 silencing on tumourigenesis as a starting point for future functional studies.

journal_name

Endocr Relat Cancer

journal_title

Endocrine-related cancer

authors

Massie CE,Spiteri I,Ross-Adams H,Luxton H,Kay J,Whitaker HC,Dunning MJ,Lamb AD,Ramos-Montoya A,Brewer DS,Cooper CS,Eeles R,UK Prostate ICGC Group.,Warren AY,Tavaré S,Neal DE,Lynch AG

doi

10.1530/ERC-14-0454

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

131-44

issue

2

eissn

1351-0088

issn

1479-6821

pii

ERC-14-0454

journal_volume

22

pub_type

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