title: Allelotypes of lung adenocarcinomas featuring ALK fusion demonstrate fewer onco- and suppressor gene changes.
abstract: BACKGROUND
  A subset of lung adenocarcinomas harboring an EML4-ALK fusion gene resulting in dominant oncogenic activity has emerged as a target for specific therapy. EML4-ALK fusion confers a characteristic histology and is detected more frequently in never or light smokers and younger patients.
  
  
  METHODS
  To gain insights into etiology and carcinogenic mechanisms we conducted analyses to compare allelotypes of 35 ALK fusion-positive and 95 -negative tumours using single nucleotide polymorphism (SNP) arrays and especially designed software which enabled precise global genomic profiling.
  
  
  RESULTS
  Overall aberration numbers (gains + losses) of chromosomal alterations were 8.42 and 9.56 in tumours with and without ALK fusion, respectively, the difference not being statistically significant, although patterns of gain and loss were distinct. Interestingly, among selected genomic regions, oncogene-related examples such as 1p34.3(MYCL1), 7q11.2(EGFR), 7p21.1, 8q24.21(MYC), 16p13.3, 17q12(ERBB2) and 17q25.1 showed significantly less gain. Also, changes in tumour suppressor gene-related regions, such as 9p21.3 (CDKN2A) 9p23-24.1 (PTPRD), 13q14.2 (RB1), were significantly fewer in tumours with ALK fusion.
  
  
  CONCLUSIONS
  Global genomic comparison with SNP arrays showed tumours with ALK fusion to have fewer alterations in oncogenes and suppressor genes despite a similar overall aberration frequency, suggesting very strong oncogenic potency of ALK activation by gene fusion.
authors.affiliation: Division of Pathology, The Cancer Institute, Ariake 3-8-31, Koutou-ku, Tokyo 135-8550, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Ninomiya
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kato
authors.forename: Masashi
authors.initials: M
authors.lastname: Sanada
authors.forename: Kengo
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Inamura
authors.forename: Noriko
authors.initials: N
authors.lastname: Motoi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nagano
authors.forename: Kimie
authors.initials: K
authors.lastname: Nomura
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Sakao
authors.forename: Sakae
authors.initials: S
authors.lastname: Okumura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mano
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000483:Alleles; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion