Abstract PR03: Somatic mutations and ancestry markers in Hispanic lung cancer patients

Abstract

Introduction: Hispanics are projected to constitute 23% of the U.S. population by 2050. However, large-scale sequencing projects, such as The Cancer Genome Atlas (TCGA), provide little information on this ethnic population. In fact, only seven out of over 500 lung adenocarcinoma tumors sequenced in the TCGA database are reported to be Hispanic. To address the lack of genomic data from Hispanic/Latino patients with lung cancer, the Latino Lung Cancer Registry was established to collect patient data and biospecimens from these patients. Methods: This retrospective observational study examined lung cancer tumor samples from 163 Hispanic/Latino patients, and tumor-derived DNA was subjected to targeted-exome sequencing (>1000 genes, including EGFR, KRAS, STK11, and TP53) and ancestry analysis. Mutation frequencies in this Hispanic/Latino cohort were compared with those in a similar cohort of non-Hispanic white (NHW) patients. Novel mutations in EGFR were functionally characterized, and mutation rates were correlated with ancestry, patient sex, smoking status, and tumor histology. Results: Among adenocarcinomas (n=120) in the Hispanic/Latino cohort, 31% had EGFR mutations versus 17% in the NHW control group (p < 0.001). The EGFR mutations in Hispanic/Latino patients included well-characterized activating mutations, such as L858R, and uncharacterized EGFR variants. A rare exon 19 mutation, W731R, was identified that conferred resistance to both erlotinib and AZD9291. KRAS (20% vs. 38%; p=0.002) and STK11 (8% vs. 16%; p=0.065) mutations occurred at lower frequency, and mutations in TP53 occurred at similar frequency (46% vs. 40%; p=0.355) in Hispanic/Latino and NHW patients, respectively. Within the Hispanic cohort, ancestry influenced the rate of TP53 mutations (p=0.009) and may influence the rate of EGFR, KRAS, and STK11 mutations. Conclusions: Driver mutations in Hispanic/Latino lung adenocarcinoma patients differ in frequency from those in NHWs associated with their Indigenous American ancestry. The spectrum of driver mutations needs to be further assessed in the Hispanic/Latino population. Citation Format: William D. Cress, Nicholas T. Gimbrone, Bhaswati Sarcar, Edna Gordian, Jason I. Rivera, Christian Lopez, Jamie K. Teer, Eric A. Welsh, Alberto A. Chiappori, Matthew B. Schabath, Gary W. Reuther, Pedro G. Santiago-Cardona. Somatic mutations and ancestry markers in Hispanic lung cancer patients [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr PR03.