title: miR-101 DNA copy loss is a prominent subtype specific event in lung cancer.
abstract: BACKGROUND
  MicroRNA-101 (miR-101) is frequently downregulated in cancer and exhibits antitumorigenic properties, suggesting that miR-101 is a putative tumor suppressor. miR-101 is encoded at two loci in the human genome: 1p31.3 (miR-101-1) and 9p24.1 (miR-101-2). We sought to investigate miR-101 locus-specific deletions and genomic loss in the major subtypes of lung cancer.
  
  
  METHODS
  Analyses of high-resolution array comparative genomic hybridization and single-nucleotide polymorphism array data were performed to determine the DNA copy number status and deletion boundaries of miR-101-1 and miR-101-2 in seven independent cohorts that comprised 1,236 lung cancer specimens and 20 lung carcinoma in situ samples. miR-101 expression was also investigated in lung cancer cell lines and tumors.
  
  
  RESULTS
  miR-101 loss at either genomic locus was identified in 29% of lung cancers analyzed and was associated with reduced miR-101 expression. Loss was more frequent at the 9p locus and occurred more often in NSCLC as opposed to small cell lung cancer. Lung carcinoma in situ also harbored miR-101 deletions, suggesting that genomic loss may be an early event in lung cancer development. Finally, miR-101 deletions on 9p were exclusive of CDKN2A deletions in several cases, providing evidence that loss of miR-101 is not merely a passenger of CDKN2A deletion.
  
  
  CONCLUSIONS
  miR-101 genomic loss occurs frequently in NSCLC and may be an early event in lung tumorigenesis. DNA deletions likely represent a prominent molecular mechanism of miR-101 downregulation in NSCLC but not in small cell lung cancer.
authors.affiliation: BC Cancer Research Centre, Vancouver, British Columbia, Canada. kthu@bccrc.ca
authors.forename: Kelsie L
authors.initials: KL
authors.lastname: Thu
authors.forename: Raj
authors.initials: R
authors.lastname: Chari
authors.forename: William W
authors.initials: WW
authors.lastname: Lockwood
authors.forename: Stephen
authors.initials: S
authors.lastname: Lam
authors.forename: Wan L
authors.initials: WL
authors.lastname: Lam
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D002278:Carcinoma in Situ / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D016147:Genes, Tumor Suppressor; D015894:Genome, Human; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D055752:Small Cell Lung Carcinoma / Q000235:genetics*
chemical_list: C534072:MIRN101 microRNA, human; D035683:MicroRNAs