title: Copy-neutral loss of heterozygosity at the p53 locus in carcinogenesis of esophageal squamous cell carcinomas associated with p53 mutations.
abstract: OBJECTIVE
  LOH at the p53 locus has been reported to be associated with esophageal squamous cell carcinogenesis. The aim of this study is to identify potential mechanisms resulting in LOH around the p53 locus in its carcinogenesis.
  
  
  METHODS
  We investigated 10 esophageal cancer cell lines and 91 surgically resected specimens, examining them for LOH at the p53 locus on chromosome 17. We examined the p53 gene by using microsatellite analysis, comparative genomic hybridization (CGH), FISH, and single-nucleotide polymorphism-CGH (SNP-CGH).
  
  
  RESULTS
  In an analysis of specimens by microsatellite markers, a close positive correlation was found between p53 mutations and LOH at the p53 locus (P < 0.01). Although four cell lines were found to be homozygous for p53 mutations, LOH at the p53 locus was not detected by CGH. Among two p53 mutant cancer cell lines and five p53 mutant/LOH cancer specimens analyzed by FISH, both the cell lines and four of the specimens exhibited no obvious copy number loss at the p53 locus. SNP-CGH analysis, which allows both determination of DNA copy number and detection of copy-neutral LOH, showed that LOHs without copy number change were caused by whole or large chromosomal alteration.
  
  
  CONCLUSIONS
  LOH without copy number change at the p53 locus was observed in p53 mutant esophageal squamous cell carcinomas. Our data suggest that copy-neutral LOH occurring as a result of chromosomal instability might be the major mechanism for inactivation of the intact allele in esophageal squamous cell carcinogenesis associated with p53 mutation.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan. h-saeki@surg2.med.kyushu-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saeki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kitao
authors.forename: Keiji
authors.initials: K
authors.lastname: Yoshinaga
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nakanoko
authors.forename: Nobuhide
authors.initials: N
authors.lastname: Kubo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kakeji
authors.forename: Masaru
authors.initials: M
authors.lastname: Morita
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D043171:Chromosomal Instability; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005787:Gene Frequency; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D019656:Loss of Heterozygosity; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53