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

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; ... (2017). Exome Sequencing of African-American Prostate Cancer Reveals Loss-of-Function ERF Mutations. Cancer discovery, 7(9), pp. 973-983. American Association for Cancer Research 10.1158/2159-8290.CD-16-0960

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie

UniBE Contributor:

Rubin, Mark Andrew

Subjects:

500 Science
500 Science > 570 Life sciences; biology

ISSN:

2159-8290

Publisher:

American Association for Cancer Research

Language:

English

Submitter:

Marla Rittiner

Date Deposited:

20 Feb 2018 11:15

Last Modified:

20 Feb 2018 11:15

Publisher DOI:

10.1158/2159-8290.CD-16-0960

PubMed ID:

28515055

URI:

https://boris.unibe.ch/id/eprint/110755

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