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


ABSTRACT: 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.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.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.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.

SUBMITTER: Araujo LH 

PROVIDER: S-EPMC4618391 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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

Araujo Luiz H LH   Lammers Philip E PE   Matthews-Smith Velmalia V   Eisenberg Rosana R   Gonzalez Adriana A   Schwartz Ann G AG   Timmers Cynthia C   Shilo Konstantin K   Zhao Weiqiang W   Natarajan Thanemozhi G TG   Zhang Jianying J   Yilmaz Ayse Selen AS   Liu Tom T   Coombes Kevin K   Carbone David P DP  

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 20151001 10


<h4>Introduction</h4>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.<h4>Methods</h4>We collected NSCLC  ...[more]

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