Demographic variation in molecular profiles of tumors from metastatic colon cancer patients.

Abstract

e15528 Background: Hispanic patients constitute one of the minority ethnic groups in metastatic colon cancer research and are underrepresented in clinical trials. The current treatment landscape for metastatic colon cancer includes targeted therapy based on the molecular profile of tumors. However, due to the under-representation of minorities in clinical trials, the prevalence of mutations in various ethnic sub-groups is unknown. We performed a retrospective study to analyze the mutational profiles of patients in central California, where nearly half the population is Hispanic. Methods: A retrospective review was conducted to determine the prevalence of mutations in a single center from January 2020 to December 2023. A total of 79 patients were evaluated of which 43 were Hispanic, 28 Caucasian, 4 African American, and 4 Asian. Molecular profile data was collected through next-generation sequencing. Results: The median age at diagnosis was sixty years old. Of the 79 patients, 42 were female, and 37 were male. 39 were right-sided, 38 were left-sided, and 2 were of indeterminate origin. 43 patients were Hispanic, and 36 patients were non-Hispanic. Out of 79 patients, 44 harbored KRAS mutations. The frequency of KRAS mutations in Hispanics was 25 (58.1%), and in non-Hispanics was 19 (52.8%). The frequency of combined NRAS and KRAS mutations was 29 (67%) in Hispanics, and 19 (52.8%) in non-Hispanics. The noted 44 KRAS mutations are listed in order of frequency, in parentheses T represents total patients, H represents Hispanic patients, and N represents Non-Hispanic patients: G12D (11T, 4H, 7N), G12V (10T, 7H, 3N), G13D (9T, 4H, 5N), G12C (5T, 3H, 2N), G12F (2T, 1H, 1N), G13R (2T, 2H, 0N), A146V (2T, 2H, 0N), A146T (1T, 0H, 1N), G12A (1T, 1H, 0N), G12S (1T, 1H, 0N). Of the 44 KRAS mutations 30 were related to codon 12 (68%), 11 related to codon 13 (25%), and 3 related to codon 146 (7%). Of the 44 KRAS mutated patients, only 5 (11%) patients harbored the targetable mutation KRAS G12C. Conclusions: This study shows that Hispanic patients harbor a high percentage of RAS mutations when compared to non-Hispanic patients, especially in older cohorts, as the median age in this studied group was 60. This study also shows that non-G12C mutations are common, especially codon 12 and codon 13 mutations. Thus, other mutations that may benefit from the development of targeted therapy include KRAS mutations G12D, G12V, and G13D. This retrospective study suggests that continued development of targeted therapy for non-KRAS G12C mutations is warranted.