Breast and Prostate Cancers Harbor Common Somatic Copy Number Alterations that Consistently Differ by Race-Ethnicity
Chen Y, Li J, Sadasivan S, She R, Datta I, Chitale D, Gupta N, Davis MB, Rogers CG, Newman LA, Paris PL, Rybicki BA, and Levin AM. Breast and Prostate Cancers Harbor Common Somatic Copy Number Alterations that Consistently Differ by Race-Ethnicity. Cancer Res 2018; 78(13)
Pan-cancer studies of somatic copy number alterations (SCNAs) have demonstrated shared SCNAs across cancer types, but whether these shared SCNAs vary by raceethnicity has not been explored. Utilizing data from The Cancer Genome Atlas (TCGA), we identified SCNAs in breast and prostate tumors, two cancers with racially-disparate outcomes, and then tested for differences in SCNA magnitude by self-reported African American and European American race-ethnicity, as well as by regional chromosomal African ancestry within African Americans. GISTIC2 was applied to high density SNP array data to map SCNA regions in 712 European and 174 African American female breast tumors and 267 European and 42 African American prostate tumors derived from the TCGA dataset. For each tumor, SCNA magnitude was quantified by the area under the logarithm-base 2 copy number curve, and the germline ancestral origin of SCNAs was inferred using RFMix. A linear model was used to assess the association between SCNA magnitude and race-ethnicity (or regional African ancestry) while adjusting age-at-diagnosis and tumor severity. Race-differentiated SCNAs common to breast and prostate were found at chromosomes 5q11-21, 6q12-14, 6q16-22, 8q21-24, 11q22, 13q12-21, and 16q21-24, with 8q21-24 being the only amplification. African American breast and prostate tumors had higher magnitude alterations in the regions on 5q11-21, 8q21-24, 11q22, and 13q12-21, and among African Americans, this higher magnitude at 8q21- 24 and 13q12-21 was consistent with increasing regional African ancestry. Within these regions with higher magnitude SCNAs in African Americans, expression analysis revealed 18 cancer genes, including RB1 and PVT1, differentially expressed by race-ethnicity in both tumors types that were consistent with the observed SCNA differences. While differences in SCNAs by race-ethnicity have been studied in single cancers, this is the first study to identify race-differentiated SCNAs shared by two hormonally-driven cancers and to explore the potential of germline genetic ancestry as a mechanism leading to this differentiation. The differentially expressed genes within SCNAs common to both tumor types could provide further insight into the racially disparate outcomes in breast and prostate cancers.