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. 2015 Oct;10(10):1430-6.
doi: 10.1097/JTO.0000000000000650.

Somatic Mutation Spectrum of Non-Small-Cell Lung Cancer in African Americans: A Pooled Analysis

Luiz H Araujo  1 , Philip E Lammers, Velmalia Matthews-Smith, Rosana Eisenberg, Adriana Gonzalez, Ann G Schwartz, Cynthia Timmers, Konstantin Shilo, Weiqiang Zhao, Thanemozhi G Natarajan, Jianying Zhang, Ayse Selen Yilmaz, Tom Liu, Kevin Coombes, David P Carbone
Affiliations

Somatic Mutation Spectrum of Non-Small-Cell Lung Cancer in African Americans: A Pooled Analysis

Luiz H Araujo et al. J Thorac Oncol. 2015 Oct.

Abstract

Introduction: The mutational profile of non-small-cell lung cancer (NSCLC) has become an important tool in tailoring therapy to patients, with clear differences according to the population of origin. African Americans (AAs) have higher lung cancer incidence and mortality than Caucasians, yet discrepant results have been reported regarding the frequency of somatic driver mutations. We hypothesized that NSCLC has a distinct mutational profile in this group.

Methods: We collected NSCLC samples resected from self-reported AAs in five sites from Tennessee, Michigan, and Ohio. Gene mutations were assessed by either SNaPshot or next generation sequencing, and ALK translocations were evaluated by fluorescence in situ hybridization.

Results: Two hundred sixty patients were included, mostly males (62.3%) and smokers (86.6%). Eighty-one samples (31.2%) were squamous cell carcinomas. The most frequently mutated genes were KRAS (15.4%), epidermal growth factor receptor (EGFR, 5.0%), PIK3CA (0.8%), BRAF, NRAS, ERBB2, and AKT1 (0.4% each). ALK translocations were detected in two nonsquamous tumors (1.7%), totaling 61 cases (23.5%) with driver oncogenic alterations. Among 179 nonsquamous samples, 54 (30.2%) presented a driver alteration. The frequency of driver alterations altogether was lower than that reported in Caucasians, whereas no difference was detected in either EGFR or KRAS mutations. Overall survival was longer among patients with EGFR mutations.

Conclusions: We demonstrated that NSCLC from AAs has a different pattern of somatic driver mutations than from Caucasians. The majority of driver alterations in this group are yet to be described, which will require more comprehensive panels and assessment of noncanonical alterations.

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Figures

Figure 1
Figure 1
Classic mutations in non-small cell lung cancer (NSCLC) and non-squamous tumors resected from African Americans.
Figure 2
Figure 2
Distribution of classic driver mutations in African Americans, with a significant pattern of mutual exclusivity.
See this image and copyright information in PMC

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