Abstract 5227: Molecular profiling in African American NSCLC patients to identify novel potential driver mutations
Authors: Schwartz Ann G. , Wenzlaff Angela S. , Lusk Chrissy M. , Dyson Greg , Bollig-Fischer Aliccia , Land Susan , Lata Sneh , Cote Michele L. , Bepler Gerold , Gadgeel Shirish M. 
Published: July 2016

African Americans continue to have poorer 5 year survival after a lung cancer diagnosis than whites for reasons that remain to be fully characterized. This disparity remains even with advances in treatments targeting specific driver mutations that have improved outcomes for some patients. Although the relative frequency of these genetic alterations varies in subsets of individuals defined by sex, histologic subtype, smoking history and race, little is known about the occurrence of these mutations in African Americans. In this study, we characterize the spectrum of known driver mutations in 200 African American NSCLC patients and seek to identify novel somatic mutations in this population. Initially, the population was screened using the Sequenom LungCarta panel of 216 mutations in 24 genes known to contain alterations associated with lung cancer, RET and ROS1 fusion gene expression, and amplification of FGFR1. Whole-exome sequencing is being performed on tumors from those patients with no known somatic mutations. Paired normal and tumor DNA/RNA samples are being genotyped to distinguish germline from somatic mutations in both the screening and sequencing phases. Initial screening has been completed on 130 patients, with the remaining 70 underway. The mean age of the patients enrolled is 61.7 years, 58.5% are female, and 8.5% are never smokers. In profiling the first 130 African American patients, we find that only 28% of patients (N = 36) carry a known somatic mutation that is not present in the germline, far lower than the 41% reported in white patients in our previous studies. Of the identified mutations, approximately 23.8% are KRAS and 23.8% are PT53 alterations. The next most frequent somatic alterations are in EGFR (16.7%). The remaining alterations occurred in only 1 or 2 tumors and include EPHA3, ERBB2, FGFR1, MET, NOTCH1, NRAS, NTRK2, PIK3CA, PTEN, RET and STK11. Five percent of patients have tumors with two driver mutations. Half of the tumors carrying 2 driver mutations had concurrent alterations in KRAS and TP53. Patients with known genetic alterations were more likely to be female than patients with no known genetic alterations (p = 0.42), but did not differ in age, smoking status, pack-years, family history of lung cancer, history of COPD, stage at diagnosis or histology. Mutations in EGFR were responsible for the differences by sex. Exome sequencing is complete for the first 48 of the 92 patients with no known somatic mutations. Sequences are being aligned using Novoalign and GATK will be used for variant calling; results will be available soon. Genetic profiling of NSCLC in African Americans has the potential to both identify novel mutations, expanding the list of potential targets for tailored treatments, and aid clinical decision making in African American patients leading to improvements in outcomes.

Citation Format: Ann G. Schwartz, Angela S. Wenzlaff, Chrissy M. Lusk, Greg Dyson, Aliccia Bollig-Fischer, Susan Land, Sneh Lata, Michele L. Cote, Gerold Bepler, Shirish M. Gadgeel. Molecular profiling in African American NSCLC patients to identify novel potential driver mutations. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5227.