Exome Sequencing of African-American Prostate Cancer Reveals Loss-of-Function ERF Mutations. Academic Article uri icon

Overview

abstract

  • African-American men have the highest incidence of and mortality from prostate cancer. Whether a biological basis exists for this disparity remains unclear. Exome sequencing (n = 102) and targeted validation (n = 90) of localized primary hormone-naïve prostate cancer in African-American men identified several gene mutations not previously observed in this context, including recurrent loss-of-function mutations in ERF, an ETS transcriptional repressor, in 5% of cases. Analysis of existing prostate cancer cohorts revealed ERF deletions in 3% of primary prostate cancers and mutations or deletions in ERF in 3% to 5% of lethal castration-resistant prostate cancers. Knockdown of ERF confers increased anchorage-independent growth and generates a gene expression signature associated with oncogenic ETS activation and androgen signaling. Together, these results suggest that ERF is a prostate cancer tumor-suppressor gene. More generally, our findings support the application of systematic cancer genomic characterization in settings of broader ancestral diversity to enhance discovery and, eventually, therapeutic applications.Significance: Systematic genomic sequencing of prostate cancer in African-American men revealed new insights into prostate cancer, including the identification of ERF as a prostate cancer gene; somatic copy-number alteration differences; and uncommon PIK3CA and PTEN alterations. This study highlights the importance of inclusion of underrepresented minorities in cancer sequencing studies. Cancer Discov; 7(9); 973-83. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 920.

authors

  • Huang, Franklin W
  • Mosquera, Juan Miguel
  • Garofalo, Andrea
  • Oh, Coyin
  • Baco, Maria
  • Amin-Mansour, Ali
  • Rabasha, Bokang
  • Bahl, Samira
  • Mullane, Stephanie A
  • Robinson, Brian D.
  • Aldubayan, Saud
  • Khani, Francesca
  • Karir, Beerinder
  • Kim, Eejung
  • Chimene-Weiss, Jeremy
  • Hofree, Matan
  • Romanel, Alessandro
  • Osborne, Joseph R.
  • Kim, Jong Wook
  • Azabdaftari, Gissou
  • Woloszynska-Read, Anna
  • Sfanos, Karen
  • De Marzo, Angelo M
  • Demichelis, Francesca
  • Gabriel, Stacey
  • Van Allen, Eliezer M
  • Mesirov, Jill
  • Tamayo, Pablo
  • Rubin, Mark A
  • Powell, Isaac J
  • Garraway, Levi A

publication date

  • May 17, 2017

Research

keywords

  • Prostatic Neoplasms
  • Repressor Proteins

Identity

PubMed Central ID

  • PMC5836784

Scopus Document Identifier

  • 85026420328

Digital Object Identifier (DOI)

  • 10.1158/2159-8290.CD-16-0960

PubMed ID

  • 28515055

Additional Document Info

volume

  • 7

issue

  • 9