Genomic Profiling of Prostate Cancers from Men with African and European Ancestry.

African American (AFR) men have the highest mortality rate from prostate cancer (PCa) compared with men of other racial/ancestral groups. Differences in the spectrum of somatic genome alterations in tumors between AFR men and other populations have not been well-characterized due to a lack of inclusion of significant numbers in genomic studies.

To identify genomic alterations associated with race, we compared the frequencies of somatic alterations in PCa obtained from four publicly available datasets comprising 250 AFR and 611 European American (EUR) men and a targeted sequencing dataset from a commercial platform of 436 AFR and 3018 EUR men.

Mutations in ZFHX3 as well as focal deletions in ETV3 were more frequent in tumors from AFR men. TP53 mutations were associated with increasing Gleason score. MYC amplifications were more frequent in tumors from AFR men with metastatic PCa, whereas deletions in PTEN and rearrangements in TMPRSS2-ERG were less frequent in tumors from AFR men. KMT2D truncations and CCND1 amplifications were more frequent in primary PCa from AFR men. Genomic features that could impact clinical decision making were not significantly different between the two groups including tumor mutation burden, MSI status, and genomic alterations in select DNA repair genes, CDK12, and in AR.

Although we identified some novel differences in AFR men compared with other populations, the frequencies of genomic alterations in current therapeutic targets for PCa were similar between AFR and EUR men, suggesting that existing precision medicine approaches could be equally beneficial if applied equitably.

Clinical cancer research : an official journal of the American Association for Cancer Research. 2020 Jul 10 [Epub ahead of print]

Yusuke Koga, Hanbing Song, Zachary R Chalmers, Justin Newberg, Eejung Kim, Jian Carrot-Zhang, Daphnee Piou, Paz Polak, Sarki A Abdulkadir, Elad Ziv, Matthew Meyerson, Garrett M Frampton, Joshua D Campbell, Franklin W Huang

Department of Medicine, Boston University School of Medicine, Boston, Massachusetts., Division of Hematology/Oncology, Department of Medicine; Helen Diller Family Comprehensive Cancer Center; Bakar Computational Health Sciences Institute; Institute for Human Genetics; San Francisco Veterans Affairs Medical Center; University of California, San Francisco, San Francisco, California., Department of Urology, Northwestern University Feinberg School of Medicine., Foundation Medicine, Cambridge, Massachusetts., Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Mount Sinai School of Medicine, New York, New York., Division of General Internal Medicine, University of California, San Francisco, San Francisco, California., Department of Medicine, Boston University School of Medicine, Boston, Massachusetts. ., Division of Hematology/Oncology, Department of Medicine; Helen Diller Family Comprehensive Cancer Center; Bakar Computational Health Sciences Institute; Institute for Human Genetics; San Francisco Veterans Affairs Medical Center; University of California, San Francisco, San Francisco, California. .

PubMed http://www.ncbi.nlm.nih.gov/pubmed/32651179


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