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Cancer Discov. 2017 Sep;7(9):973-983. doi: 10.1158/2159-8290.CD-16-0960. Epub 2017 May 17.

Exome Sequencing of African-American Prostate Cancer Reveals Loss-of-Function ERF Mutations.

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. levi_garraway@dfci.harvard.edu franklin_huang@dfci.harvard.edu ipowell@med.wayne.edu rubinma@med.cornell.edu.
2
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
3
Cancer Program, the Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
4
Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian, New York, New York.
5
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
6
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
7
Centre for Integrative Biology, University of Trento, Trento, Italy.
8
Department of Radiology, Weill Cornell Medicine, New York, New York.
9
Department of Pathology, Roswell Park Cancer Institute, Roswell Park, New York.
10
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Roswell Park, New York.
11
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
12
Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
13
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
14
Department of Medicine, University of California, San Diego, La Jolla, California.
15
Moores Cancer Center, University of California, San Diego, La Jolla, California.
16
Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine-New York Presbyterian, New York, New York. levi_garraway@dfci.harvard.edu franklin_huang@dfci.harvard.edu ipowell@med.wayne.edu rubinma@med.cornell.edu.
17
Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, New York.
18
Barbara Ann Karmanos Cancer Institute, Detroit, Michigan. levi_garraway@dfci.harvard.edu franklin_huang@dfci.harvard.edu ipowell@med.wayne.edu rubinma@med.cornell.edu.
19
Department of Urology, Wayne State University School of Medicine, Detroit, Michigan.

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.

PMID:
28515055
PMCID:
PMC5836784
DOI:
10.1158/2159-8290.CD-16-0960
[Indexed for MEDLINE]
Free PMC Article

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