Multiplex testing of driver mutations in non-small cell lung cancer (NSCLCs) of African-American (AA) patients.

Abstract

7561 Background: Recently driver genetic alterations have been identified in NSCLC that can be targeted for therapeutic interventions. Previous reports have suggested that rates of certain mutations may vary according to ethnic background. We conducted multiplex testing of NSCLCs of AA and white patients to assess variability in the mutation rates by race. Methods: We identified tumor tissues of 136 AA and 320 white NSCLC patients collected as part of three different institutional review board approved studies. Using the Sequenom MassArray system and a multiplexed panel, we analyzed tumor DNA for 214 oncogenic mutations in 26 genes previously identified in NSCLC. Estimated risk (Odds Ratios (OR)) of any mutation and specific gene mutations among AA patients compared to white patients were calculated after adjusting for age, sex, smoking status and histology (adenocarcinoma versus non-adenocarcinoma). Information on smoking status was unavailable on 46 patients and was not included in calculations of ORs for some genes (ORª). Results: The median age at diagnosis was 60 vs 66 years in AA vs white patients; 43% of AA patients and 66% of white patients were males; 69% of AA patients and 52% of white patients had adenocarcinoma; 66% of AA patients and 85% of white patients had stage I/II NSCLC and 10% of AA patients and 6% of white patients were never smokers. 43% of the AA patients and 47% of white patients had at least one mutation detected (OR = 0.78; 0.5-1.2). 19% of AA patients and 6% of white patients had more than 1 mutation detected (OR 2.3; 1.1-4.9). AA patients were more likely to harbor mutations in STK11 (LKB1) (OR=8.4; 3.2-21.8) and NOTCH1 (ORª=8.1; 2.2-30.8), and they were less likely to have MET mutations (ORª= 0.12; 0.02-0.9) then white patients. While not statistically significant, AA had lower prevalence of Kras mutations (OR=0.64, 0.3-1.4) and p53 mutations (OR= 0.82; 0.4-1.6). Conclusions: Our analysis of NSCLCs shows that AAs were more likely to have multiple genetic mutations than whites and the mutation profile differs by race.