Abstract B066: Breast and prostate cancers harbor common somatic copy number alterations that consistently differ by race and are associated with survival

Abstract

Abstract African Americans (AAs) tend to have more aggressive diseases and worse outcomes for many cancer types compared to European Americans (EAs). Large structural changes on chromosomes, such as somatic copy number alterations (SCNAs), are commonly present in many cancers and associated with clinical outcomes. While studies focusing on single tumor types have identified racial differences in SCNA frequencies and their possible association with cancer outcomes, pan-cancer race-differentiated SCNAs and their clinical implications have not been fully explored. Focusing on two of the most common hormonally driven cancers, breast cancer in women and prostate cancer in men, and using data from The Cancer Genome Atlas (TCGA), we first identified recurrent SCNAs using GISTIC2 in AAs and EAs separately within each cancer. For each GISTIC2 identified SCNA region, we calculated the magnitude deviation from the expected null value (i.e. copy number (CN) = 2) using the area under the log2(CN) (cnAUC) for each tumor. Modeling cnAUC as the outcome variable, we identified SCNAs that differed between AAs and EAs in breast cancers (n=58 SCNAs; permutation p<10-4) and prostate cancers (n=78 SCNAs; permutation p=0.006). Six of nine race-differentiated SCNAs common to breast and prostate cancers had consistent magnitude differences by race across both tumor types, and all six were of higher magnitude in AAs. These six race-differentiated SCNAs were found at chromosomes 5q11.2-q14.1, 5q15-q21.1, 8q21.11-q21.13, 8q21.3-q24.3, 11q22.3, and 13q12.3-q21.3 with the chromosome 8q regions being the only amplifications. Unsupervised hierarchical clustering of the SCNAs in these six race-differentiated regions identified three patient groups in each tumor type with significant survival differences. Of particular importance, within triple negative breast cancers, these SCNA patient groups showed the most significant difference in progression-free survival (p=0.019). While there was a higher frequency of AAs among the SCNA-defined patient groups with worse survival, no significant racial difference in survival was observed within each SCNA-defined patient group. This observation supports the idea that racial disparities in breast and prostate cancer outcomes might be in part due to racial differences in tumor biology that drive structural chromosomal changes shared across these common tumor types. Our ability to derive SCNA defined patient groups associated with survival based on race-differentiated genomic aberrations demonstrates both their clinical relevance and the need to understand the biologic mechanisms that give rise to them. Citation Format: Yalei Chen, Sudha M Sadasivan, Ruicong She, Indrani Datta, Kanika Taneja, Chitale Dhananjay, Nilesh Gupta, Melissa B Davis, Lisa A Newman, Craig G Rogers, Pamela L Paris, Jia Li, Benjamin A Rybicki, Albert M Levin. Breast and prostate cancers harbor common somatic copy number alterations that consistently differ by race and are associated with survival [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B066.