title: MYC amplification as a prognostic marker of early-stage lung adenocarcinoma identified by whole genome copy number analysis.
abstract: OBJECTIVE
  Even in small-sized (≤ 2 cm in greatest dimension) and/or pathologic stage I lung adenocarcinoma (ADC), a considerable proportion of the patients will relapse within 5 years and show poor prognosis. The purpose of this study was to identify genetic alterations that define prognosis of patients with early-stage lung ADC.
  
  
  METHODS
  Regions of copy number alterations in 65 small-sized lung ADCs and 40 ADC cell lines were determined by using GeneChip Human Mapping 10-K and 250-K single-nucleotide polymorphism (SNP) arrays, respectively. A copy number assay based on real-time genomic PCR (RT-G-PCR) was done for 60 small-sized lung ADCs and 162 stage I lung ADCs.
  
  
  RESULTS
  Several regions on chromosomes 5p, 7p, 8q, and 14q were frequently (>10%) amplified in both small-sized ADCs and lung ADC cell lines. In particular, the MYC gene was mapped in the minimum common region at chromosome 8q24.21, and therefore was indicated to be a target of gene amplification in lung ADCs. MYC amplification correlated with poor prognosis (P = 0.031) of patients with small-sized ADCs. MYC amplification detected by SNP array analysis was well reproduced by RT-G-PCR analysis. Therefore, to investigate the utility of MYC amplification as a prognostic marker for early-stage lung ADCs, 162 stage I lung ADCs were subjected to the analysis. MYC amplification was associated with relapse-free survival in these patients (P = 0.013 by multivariate Cox proportional hazard model analysis).
  
  
  CONCLUSIONS
  These results strongly indicate that MYC amplification is a prognostic marker of patients with early-stage lung ADCs.
authors.affiliation: Biology Division, National Cancer Center Research Institute; Cancer Genomics Project, The University of Tokyo, Tokyo, Japan.
authors.forename: Reika
authors.initials: R
authors.lastname: Iwakawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kato
authors.forename: Kouya
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
authors.forename: Masayuki
authors.initials: M
authors.lastname: Noguchi
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Jun
authors.initials: J
authors.lastname: Yokota
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D002875:Chromosomes / Q000648:ultrastructure; D018572:Disease-Free Survival; D005784:Gene Amplification; D018628:Gene Dosage; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008495:Medical Oncology / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016271:Proto-Oncogene Proteins c-myc