Abstract C085: Somatic mutational profiles of breast tumors from Hispanic/Latino women

Abstract Background: Breast cancer is the leading cause of cancer mortality among Hispanic/Latina (H/L) women. Precision medicine holds promise for more effective treatments by targeting therapies based on somatic mutations, copy number changes, mutational signatures, and/or germline risk variants. However, there is a paucity of genomics data for H/L women with breast cancer leading to a disparity in the application of precision medicine. We have previously characterized mutational profiles of 146 breast tumors from 140 H/L women. Here, we analyze data from whole exome tumor/normal sequencing and tumor RNA sequencing from 430 self-reported H/L breast cancer cases and compare their profiles to 385 tumors from self-reported White breast cancer cases. Methods: All participants were treated at City of Hope and all sequencing data were generated using Ashion GEM ExTra (Exact Sciences). Tumor/germline sequence data were aligned to the human genome (Build37) and variants were called using the FreeBayes workflow. To determine significantly mutated genes, we used MutSigCV and dNdS. We used Fisher’s exact test to determine if the frequency of somatic mutations was significantly different among H/L women and White women and corrected for multiple hypothesis testing using Benjamini-Hochberg false discovery rate (FDR). Results: Seventeen genes and 19 genes had q-values < 0.05 in H/L and White samples, respectively. Of those, AKT1, CBFB, FOXA1, MAP2K4, MAP3K1, MLL3, PIK3CA, PTEN, RB1, RUNX1, TBX3, TP53, and ZFPM1 were significantly mutated in both. CTCF and HS6ST1 were significantly mutated only in tumors from H/L. ARID1A, CDKN1B, NCOR1, and PRRT2 were significantly mutated only in tumors from White women. There was a significantly higher frequency of TP53 mutations (FDR q-value = 0.007) and CTCF mutations (FDR q-value = 0.057) in tumors from H/L compared to tumors from Whites. Conclusions: We found TP53 and CTCF to be more commonly mutated in tumors from H/L women. CTCF mutations are seen in other tumor types, but our study is the first to demonstrate that this gene is significantly mutated in breast cancer in any population. Since CTCF is a broadly active transcriptional regulator, tumors with these mutations may be associated with broad dysregulation of gene expression. Citation Format: Yuan Chun Ding, Shu Tao, Allen Mao, Elad Ziv, Susan L. Neuhausen. Somatic mutational profiles of breast tumors from Hispanic/Latino women [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C085.