Nowinski, S;
Santaolalla, A;
O'Leary, B;
Loda, M;
Mirchandani, A;
Emberton, M;
Van Hemelrijck, M;
(2018)
Systematic identification of functionally relevant risk alleles to stratify aggressive versus indolent prostate cancer.
Oncotarget
, 9
(16)
pp. 12812-12824.
10.18632/oncotarget.24400.
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Abstract
Novel approaches for classification, including molecular features, are needed to direct therapy for men with low-grade prostate cancer (PCa), especially men on active surveillance. Risk alleles identified from genome-wide association studies (GWAS) could improve prognostication. Those risk alleles that coincided with genes and somatic copy number aberrations associated with progression of PCa were selected as the most relevant for prognostication. In a systematic literature review, a total of 698 studies were collated. Fifty-three unique SNPs residing in 29 genomic regions, including 8q24, 10q11 and 19q13, were associated with PCa progression. Functional studies implicated 21 of these single nucleotide polymorphisms (SNPs) as modulating the expression of genes in the androgen receptor pathway and several other oncogenes. In particular, 8q24, encompassingMYC, harbours a high density of SNPs conferring unfavourable pathological characteristics in low-grade PCa, while a copy number gain ofMYCin low-grade PCa was associated with prostate-specific antigen recurrence after radical prostatectomy. By combining GWAS data with gene expression and structural rearrangements, risk alleles were identified that could provide a new basis for developing a prognostication tool to guide therapy for men with early prostate cancer.
| Type: | Article |
|---|---|
| Title: | Systematic identification of functionally relevant risk alleles to stratify aggressive versus indolent prostate cancer |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.18632/oncotarget.24400 |
| Publisher version: | https://doi.org/10.18632/oncotarget.24400 |
| Language: | English |
| Additional information: | This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | GWAS, active surveillance, functional risk alleles, prostate cancer, somatic copy number aberrations |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10045879 |
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