Abstract

Abstract Background and Hypothesis: Lung cancer is the leading cause of cancer-related deaths in the United States. The reasons for higher incidence and inferior survival rates among African American lung cancer patients have not been adequately defined. We hypothesized that molecular differences, specifically differential incidence of somatic cancer gene mutations, may be a contributing factor to these population-based disparities. Large-scale, high-throughput genomic studies of the major subtype of lung cancer, non-small cell lung cancer (NSCLC), have so far neglected to adequately represent African American patients. Such information holds potential to transform treatment decisions to improve care for subsets of patients and address disparities. Methods: We tested our hypothesis using a MALDI-TOF mass spectrometry approach to analyze tumor DNA for 214 coding mutations in 26 cancer genes previously linked to NSCLC, including oncogenes and tumor suppressor genes. The sample sets investigated included NSCLC specimens from 335 patients of European ancestry and 137 African Americans. For 299 of these 472, DNA from normal matched specimens was available and included in the study, thus totaling 771 samples. Results: There was no significant difference in frequencies for somatic cancer gene coding mutations across populations and gene mutation frequencies were within reported ranges, e.g., KRAS (11%), EGFR (10%) and PIK3CA (2%). However, this study also uncovered a previously unrecognized germ line variant in the DDR2 oncogene. In addition, we found that the frequencies of single nucleotide polymorphisms (SNPs) in STK11, cMet, and NOTCH differ between African American and European ancestry patients. Conclusion: This body of work is among the largest reported on to date comparing somatic cancer gene mutations in African American and European-ancestry patients. The outcomes show that across a broad spectrum of coding mutations, genomic tumor testing could equally benefit both populations. Citation Format: Aliccia Bollig-Fischer, Shirish Gadgeel, Wei Chen, Michele Cote, Ann G. Schwartz, Gerold Bepler. Characterizing cancer gene mutations in non-small cell lung cancer from African American patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 258. doi:10.1158/1538-7445.AM2014-258

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