Systematic identification of functionally relevant risk alleles to stratify aggressive versus indolent prostate cancer

TY - JOUR

T1 - Systematic identification of functionally relevant risk alleles to stratify aggressive versus indolent prostate cancer

AU - Nowinski, Salpie Elena

AU - Santa Olalla, Aida

AU - O’Leary, Ben

AU - Loda, Massimo

AU - Mirchandani, Ayesha

AU - Emberton, Mark

AU - Van Hemelrijck, Mieke

AU - Grigoriadis, Anita

PY - 2018/2/5

Y1 - 2018/2/5

N2 - 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, encompassing MYC, harbours a high density of SNPs conferring unfavourable pathological characteristics in low-grade PCa, while a copy number gain of MYC in 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.

AB - 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, encompassing MYC, harbours a high density of SNPs conferring unfavourable pathological characteristics in low-grade PCa, while a copy number gain of MYC in 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.

UR - http://www.scopus.com/inward/record.url?scp=85042559557&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.24400

DO - 10.18632/oncotarget.24400

M3 - Article

SN - 1949-2553

VL - 9

SP - 12812

EP - 12824

JO - Oncotarget

JF - Oncotarget

ER -