Abstract C171: Identifying cancer driver mutation signatures in lung adenocarcinoma from Black/African American individuals: Addressing cancer health disparities

Abstract Lung cancer remains the leading cause of cancer-related mortality globally and continues to contribute significantly to cancer health disparities. Black/African American (B/AA) men exhibit a higher risk of lung cancer compared to White men; B/AA individuals also exhibit lower 5-year survival and stage-specific survival rates than White subjects. Biological factors, including genetic differences in cancer driver mutation, may influence this disparity. Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer across all ethnic groups, including B/AA individuals. Our study aims to characterize the main driver and co-mutation signatures of LUAD in B/AA individuals, who are significantly underrepresented in current mutational studies. We hypothesize that B/AA individuals will have a unique repertoire of cancer driver genes, which could contribute to genetic differences and response to targeted therapies compared to LUAD of White subjects. We are obtaining 100 de-identified archival formalin-fixed, paraffin-embedded (FFPE) LUAD samples from B/AA subjects from cancer registries in Florida and California. Extraction of DNA from the FFPE samples is in progress, and samples have been sent for whole exome sequencing (WES) and ancestry determination. This data will then be analyzed and compared with known LUAD mutation profiles from other ethnicities. Identification of cancer driver mutations will then inform the development of in vitro models for therapeutic testing. To date, the limited information on cancer driver genes in LUAD from B/AA subjects suggests that KRAS is the most common cancer driver gene, just like in LUAD from White subjects, and is found in ∼34% of cases. Therefore, we anticipate identifying KRAS mutations similar to this proportion based on the collection of previously published literature analyses. One key goal of this study is to obtain more information about the exact spectrum of KRAS mutations in LUAD from B/AA subjects. In addition, our work may unveil new variants of known cancer driver mutations such as KRAS, EGFR, BRAF, etc., and finally, “new” driver genes. Our efforts will address critical gaps in the understanding of lung cancer driver genes, a key step to developing personalized treatment of lung cancer and mitigating cancer health disparities between B/AA and White individuals. Supported by grants U54CA233396, U54CA233444, and U54CA233465 from the National Institutes of Health (NIH)/National Cancer Institute (NCI), the Norris Comprehensive Cancer Center core grant, award number P30CA014089 from the NIH/NCI, and by the Undergraduate Research Associates Program supported by the USC Provost. Citation Format: Davin Pan, Daniel J. Mullen, Colton Stensrud, Jose Aparicio, Christina M. Gobin, Sofia Lugo, Kweku Ofosu-Asante, Justin K. Mensah-Mamfo, Kyle R Phillips, Yong Huang, Nazarius S. Lamango, William D Wallace, Suhn K Rhie, Kristinanna M. Fredenburg, Ite A. Offringa. Identifying cancer driver mutation signatures in lung adenocarcinoma from Black/African American individuals: Addressing cancer health disparities 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 C171.