Abstract 3508: FOXA1 genetic alterations in whites versus blacks or African Americans in breast and prostate cancer
Authors: Torres Jennifer , Thangavel Hariprasad , Fu Xiaoyong , Schiff Rachel , Trivedi Meghana V. 
Published: September 2020

Forkhead box A1 (FOXA1) is a pioneer factor for the nuclear hormone receptors: estrogen receptor and androgen receptor. FOXA1 plays a major role inducing endocrine resistance in breast cancer (BC) and prostate cancer (PC), the two most prevalent cancers in the United States. In this study, we investigated FOXA1 gene alterations across different race and ethnicity using the TCGA PanCan Atlas dataset for BC and PC patients. The BC and PC dataset included 1084 and 494 patient samples, respectively, profiled for copy number alterations (CNA), gene expression, and mutations. In the BC dataset, the samples were from 877 non-Hispanic (81%), 38 Hispanic (3.5%) and 169 patients with no ethnicity data (15.5%). Among them, the majority of patients were White (n=751, 69.3%) followed by Black/African American (AA) (n=182, 16.8%), Asian (n=60, 5.5%), and American Indian or Alaska Native (n=1, 0.09%). Ninety BC patients (8.3%) had no race information. The PC dataset included 152 non-Hispanic (30.8%), 0 Hispanic, and 342 patients with no ethnicity data (69.2%). The samples obtained for the PC study were from White (n=147, 29.8%), Black/AA (n=7, 1.4%), and Asian (n=2, 0.4%) patients. Majority of the PC patients had no racial information (n=338, 68.4%) recorded. In the BC dataset, the incidence of FOXA1 alterations was 16/1070 (1.5%) CNA 24/1082 (2.2%) high mRNA expression, and 31/1066 (2.9%) mutations. Only amplifications were found within the BC patients. In the PC dataset, there were 15/489 (3.1%) CNA, 16/493 (3.2%) high mRNA expression, and 28/494 (5.7%) mutations reported in FOXA1. Deep deletion was found in one of the PC patients while the rest had amplifications. Due to insufficient numbers of Hispanic patients in the datasets, we compared the incidence of various FOXA1 alterations in White vs. Black/AA population using Fisher's exact test. Only FOXA1 mutation rate was significantly higher (p =0.03) in Blacks/AA (2/7, 28.6%) compared to Whites (5/147, 3.4%) in PC, but not in the BC dataset. Comparing the separate results of the FOXA1 CNA and gene overexpression White vs. Black/AA patients were statistically significant in both BC and PC datasets. A majority of FOXA1 mutations were missense mutations with a few frame shifts in BC and PC. The missense mutation reported in both BC and PC datasets were D226G, D226N, and H247Y. Additional studies are necessary to understand the functional significance of these mutations on the development of cancer. Complete and larger datasets that include the race and ethnicity

information from diverse group of patients as well as tumor molecular subtyping are also needed for the assessment of the mechanism of health disparity in BC and PC in minority population in the United States.

Citation Format: Jennifer Torres, Hariprasad Thangavel, Xiaoyong Fu, Rachel Schiff, Meghana V. Trivedi. FOXA1 genetic alterations in whites versus blacks or African Americans in breast and prostate cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3508.