title: Genomic profiles specific to patient ethnicity in lung adenocarcinoma.
abstract: OBJECTIVE
  East-Asian (EA) patients with non-small-cell lung cancer (NSCLC) are associated with a high proportion of nonsmoking women, epidermal growth factor receptor (EGFR)-activating somatic mutations, and clinical responses to tyrosine kinase inhibitors. We sought to identify novel molecular differences between NSCLCs from EA and Western European (WE) patients.
  
  
  METHODS
  A total of 226 lung adenocarcinoma samples from EA (n = 90) and WE (n = 136) patients were analyzed for copy number aberrations (CNA) by using a common high-resolution SNP (single nucleotide polymorphism) microarray platform. Univariate and multivariate analyses were carried out to identify CNAs specifically related to smoking history, EGFR mutation status, and ethnicity.
  
  
  RESULTS
  The overall genomic profiles of adenocarcinomas from EA and WE patients were highly similar. Univariate analyses revealed several CNAs significantly associated with ethnicity, EGFR mutation, and smoking, but not to gender, and KRAS or p53 mutations. A multivariate model identified four ethnic-specific recurrent CNAs-significantly higher rates of copy number gain were observed on 16p13.13 and 16p13.11 in EA tumors, whereas higher rates of genomic loss on 19p13.3 and 19p13.11 were observed in tumors from WE patients. We identified several potential driver genes in these regions, showing a positive correlation between cis-localized copy number changes and transcriptomic changes.
  
  
  CONCLUSIONS
  16p copy number gains (EA) and 19p losses (WE) are ethnic-specific chromosomal aberrations in lung adenocarcinoma. Patient ethnicity should be considered when evaluating future NSCLC therapies targeting genes located on these areas.
authors.affiliation: Genome Institute of Singapore, Genome, Singapore. broetp@gis.a-star.edu.sg
authors.forename: Philippe
authors.initials: P
authors.lastname: Broët
authors.forename: Cyril
authors.initials: C
authors.lastname: Dalmasso
authors.forename: Eng Huat
authors.initials: EH
authors.lastname: Tan
authors.forename: Marco
authors.initials: M
authors.lastname: Alifano
authors.forename: Shenli
authors.initials: S
authors.lastname: Zhang
authors.forename: Jeanie
authors.initials: J
authors.lastname: Wu
authors.forename: Ming Hui
authors.initials: MH
authors.lastname: Lee
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Régnard
authors.forename: Darren
authors.initials: D
authors.lastname: Lim
authors.forename: Heng Nung
authors.initials: HN
authors.lastname: Koong
authors.forename: Thirugnanam
authors.initials: T
authors.lastname: Agasthian
authors.forename: Lance D
authors.initials: LD
authors.lastname: Miller
authors.forename: Elaine
authors.initials: E
authors.lastname: Lim
authors.forename: Sophie
authors.initials: S
authors.lastname: Camilleri-Broët
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
mesh_terms: D000230:Adenocarcinoma / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D005060:Europe; D005202:Asia, Eastern; D005260:Female; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors