Abstract 3886: Comparing the mutational landscape of African American and Caucasian lung cancers

Abstract

Abstract Background: The overall death rate from lung cancer is higher in African-Americans (AA) compared to Caucasians (CAU). Understanding differences in the prevalence and type of somatic alterations between races may illuminate differences in prognosis and lead to the reduction of outcome disparities by more precisely targeting patients’ treatment. Methods: Formalin-fixed paraffin embedded tumor samples were collected from Baptist Cancer Center, Memphis, TN. DNA was extracted and sonicated to 250 bp following Covaris FFPE DNA Extraction & Purification protocol and further purified using Agencourt AMPure XP beads. The OncoPanel_v2 target enrichment panel (Agilent SureSelect) was used for hybrid capture of 502 cancer-related genes. Samples were pooled and sequenced on an Illumina HiSeq2500 to a mean depth of coverage of 210x. Tumors with >30x sequencing depth over >80% of targeted bases were considered for analysis. MuTect and SomaticIndelDetector were used to identify somatic single nucleotide variants (SNVs) and short insertions or deletions (indels), respectively. As matched normal DNA was not available for these samples, analysis was limited to variants previously observed in tumors as described in the Catalogue of Somatic Mutations in Cancer (COSMIC) database, and variants were excluded if found in the germline dataset of the Exome Sequencing Project (ESP). Results: 510 tumor specimens from 242 Black and 268 White patients (with self-reported race) were analyzed including 320 adenocarcinomas and 142 squamous cell carcinomas. Pathological classification was independently reviewed and confirmed for 374 of 472 cases for an overall concordance rate of 79%. Using principle component analysis (PCA) on germline SNVs, we observed that the biological ancestry was different than the self-reported race for 1.5% of patients. Mutational frequencies for genes with known roles in adenocarcinoma such as KRAS and EGFR were not significantly different between tumors from Black and White patients (Fisher's exact p-value > 0.05). Amplification rates for NKX2-1, MET, MDM2, and MYC and homozygous deletion rates for CDKN2A were also not significantly different between populations. Translocations involving ALK and ROS1 were detected in tumors from Black patients demonstrating that these events are present in both populations. Similarly, mutational frequencies for genes such as PIK3CA and PTEN were not significantly different across populations in squamous cell carcinomas. Conclusions: These results demonstrate that lung cancers from Black patients are more similar to Whites than East Asians with respect to genes such as EGFR, and suggest that clinical trials of targeted therapies could significantly benefit patients in both populations. Citation Format: Joshua Campbell, Christopher Lathan, Lynette Sholl, Matthew Ducar, Mikenah Vega, Ling Lin, Aaron Thorner, Nick Faris, Paul van Hummelen, Raymond Osarogiagbon, Matthew Meyerson, Laura MacConaill. Comparing the mutational landscape of African American and Caucasian lung cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3886. doi:10.1158/1538-7445.AM2015-3886