title: Somatic Mutation Spectrum of Non-Small-Cell Lung Cancer in African Americans: A Pooled Analysis.
abstract: BACKGROUND
  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.
authors: *Department of Internal Medicine, James Thoracic Center, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio; †Department of Internal Medicine, Meharry Medical College, Nashville, Tennessee; ‡Department of Internal Medicine, Baptist Center for Cancer Care, Columbus, Mississippi; §Department of Pathology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee; ‖Pathology Associates of Saint Thomas, Nashville, Tennessee; ¶Department of Internal Medicine, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan; #GenomOncology, Cleveland, Ohio; ††Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio; and ‡‡Department of Biomedical Informatics, Biomedical Informatics Shared Resource, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
authors: Luiz H
authors: LH
authors: Araujo
authors: Philip E
authors: PE
authors: Lammers
authors: Velmalia
authors: V
authors: Matthews-Smith
authors: Rosana
authors: R
authors: Eisenberg
authors: Adriana
authors: A
authors: Gonzalez
authors: Ann G
authors: AG
authors: Schwartz
authors: Cynthia
authors: C
authors: Timmers
authors: Konstantin
authors: K
authors: Shilo
authors: Weiqiang
authors: W
authors: Zhao
authors: Thanemozhi G
authors: TG
authors: Natarajan
authors: Jianying
authors: J
authors: Zhang
authors: Ayse Selen
authors: AS
authors: Yilmaz
authors: Tom
authors: T
authors: Liu
authors: Kevin
authors: K
authors: Coombes
authors: David P
authors: DP
authors: Carbone
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors