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A rare variant in EZH2 is associated with prostate cancer risk
Citation
Raspin, K and Fitzgerald, LM and Marthick, JR and Field, MA and Malley, RC and Banks, A and Donovan, S and Thomson, RJ and Foley, GR and Stanford, JL and Dickinson, JL, A rare variant in EZH2 is associated with prostate cancer risk, International Journal of Cancer pp. 1-11. ISSN 0020-7136 (2021) [Refereed Article]
Copyright Statement
© 2021 Union for International Cancer Control.
Abstract
Prostate cancer (PrCa) is highly heritable, and although rare variants contribute significantly to PrCa risk, few have been identified to date. Herein, whole-genome
sequencing was performed in a large PrCa family featuring multiple affected relatives
spanning several generations. A rare, predicted splice site EZH2 variant, rs78589034
(G > A), was identified as segregating with disease in all but two individuals in the
family, one of whom was affected with lymphoma and bowel cancer and a female relative. This variant was significantly associated with disease risk in combined familial
and sporadic PrCa datasets (n = 1551; odds ratio [OR] = 3.55, P = 1.20 × 10−5
).
Transcriptome analysis was performed on prostate tumour needle biopsies available
for two rare variant carriers and two wild-type cases. Although no allele-dependent
differences were detected in EZH2 transcripts, a distinct differential gene expression
signature was observed when comparing prostate tissue from the rare variant carriers
with the wild-type samples. The gene expression signature comprised known downstream targets of EZH2 and included the top-ranked genes, DUSP1, FOS, JUNB and
EGR1, which were subsequently validated by qPCR. These data provide evidence that
rs78589034 is associated with increased PrCa risk in Tasmanian men and further,
that this variant may be associated with perturbed EZH2 function in prostate tissue.
Disrupted EZH2 function is a driver of tumourigenesis in several cancers, including
prostate, and is of significant interest as a therapeutic target.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | genetic susceptibility, prostate cancer, rare genetic variants, transcriptome analysis |
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Oncology and carcinogenesis |
| Research Field: | Cancer genetics |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Diagnosis of human diseases and conditions |
| UTAS Author: | Raspin, K (Dr Kelsie Raspin) |
| UTAS Author: | Fitzgerald, LM (Dr Liesel FitzGerald) |
| UTAS Author: | Marthick, JR (Mr James Marthick) |
| UTAS Author: | Malley, RC (Dr Roslyn Malley) |
| UTAS Author: | Banks, A (Mrs Annette Banks) |
| UTAS Author: | Foley, GR (Miss Georgea Foley) |
| UTAS Author: | Dickinson, JL (Professor Joanne Dickinson) |
| ID Code: | 144302 |
| Year Published: | 2021 |
| Web of Science® Times Cited: | 3 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2021-05-11 |
| Last Modified: | 2022-08-29 |
| Downloads: | 0 |
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