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Cancer Discov DOI:10.1158/2159-8290.CD-16-0960

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

Publication TypeJournal Article
Year of Publication2017
AuthorsHuang, FW, Mosquera, JMiguel, Garofalo, A, Oh, C, Baco, M, Amin-Mansour, A, Rabasha, B, Bahl, S, Mullane, SA, Robinson, BD, AlDubayan, S, Khani, F, Karir, B, Kim, E, Chimene-Weiss, J, Hofree, M, Romanel, A, Osborne, JR, Kim, JWook, Azabdaftari, G, Woloszynska-Read, A, Sfanos, K, De Marzo, AM, Demichelis, F, Gabriel, S, Van Allen, EM, Mesirov, J, Tamayo, P, Rubin, MA, Powell, IJ, Garraway, LA
JournalCancer Discov
Date Published2017 May 17

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); 1-11. ©2017 AACR.


Alternate JournalCancer Discov
PubMed ID28515055