Abstract C063: Frequency and spectrum of KRAS mutations in lung adenocarcinoma from Black/African American and White/European patients
Authors: Mullen Daniel J. , Puente Pablo E. , Leon Christopher , Romero Diana I. , Ofosu-Asante Kweku , Huang Yong , Lamango Nazarius S. , Offringa Ite A. 
Published: December 2023

Abstract
Lung cancer is the most common cause of cancer death in the United States and a major source of cancer health disparity. Lung cancer incidence and mortality rates are higher in Black/African American (B/AA) men than in men from other racial/ethnic groups. Lung adenocarcinoma, arising in the alveoli or air sacs of the lung, is the most common subtype of lung cancer in all ethnic/racial groups. Genetic driver mutations can differ among racial/ethnic groups, in the identity of the mutated genes, their mutation frequencies, and the spectrum of mutations for each given gene. In addition, the same mutation could have different effects depending on an individual patient’s genetic background, resulting in differential responses to therapies. Therefore, it is important to identify the frequency and spectrum of driver mutations in different population groups. Protooncogenes from the RAS family, KRAS, NRAS, and HRAS, play a crucial role in cell growth regulation, cell proliferation, and survival. KRAS is frequently mutated in numerous cancer types, including lung adenocarcinoma, and has been reported to be the driver gene in ~30% of lung adenocarcinomas from White/European (W/E) patients. Due to the much lower number of lung cancer samples analyzed from B/AA patients, it has been unclear if the KRAS mutational frequency and spectrum in B/AA lung adenocarcinoma patients differs from that in W/E patients. Here we collected available existing data sets with mutational information on KRAS muations in lung adenocarcinoma from B/AA and W/E patients. We obtained data for 1555 B/AA and 13840 White lung adenocarcinoma patients. While B/AA lung adenocarcinoma patients had a lower prevalence of KRAS mutations (27% vs. 35%) than W/E patients, (χ2 p-value= 5.877e-10), KRAS was still the most frequently mutated cancer driver gene in both groups. The most common KRAS mutations in both B/AA and W/E patients were alterations of glycine 12 to cysteine (G12C), valine (G12V), aspartic acid (G12D), and alanine (G12A), as well as glutamine 61 to histidine (Q61H) and glycine 13 to cysteine (G13C). Given that a substantial proportion of lung adenocarcinoma patients carry a mutated KRAS gene, investigating new potential KRAS-targeting therapies remains especially urgent. To this end, we are investigating polyisoprenylated cysteinyl amide inhibitors (PCAIs), a group of potential cancer therapy agents designed to specifically disrupt and suppress hyperactive G-protein signaling, as caused by mutated RAS proteins. We are testing PCAI efficiacy on B/AA and W/E lung adenocarcinoma cell lines carrying various KRAS mutations.
Citation Format: Daniel J. Mullen, Pablo E. Puente, Christopher Leon, Diana I. Romero, Kweku Ofosu-Asante, Yong Huang, Nazarius S. Lamango, Ite A. Offringa. Frequency and spectrum of KRAS mutations in lung adenocarcinoma from Black/African American and White/European patients [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C063.