title: Chromosomal and microsatellite instability in sporadic gastric cancer.
abstract: BACKGROUND
  Gastric cancer can progress through two pathways of genomic instability: chromosomal (CIN) and microsatellite instability (MSI). It is hypothesized that these two pathways are not always independent and that some tumors show overlap between these two mechanisms.
  
  
  METHODS
  A total of 98 sporadic gastric cancers were classified based on their MSI status, using microsatellite assay with BAT26. Evidence for CIN was investigated by identifying loss of heterozygosity (LOH) events on chromosome arms, 5q, 10p, 17p, 17q, and 18q, which are regions harboring tumor suppressor genes that are significant in gastric cancer development.
  
  
  RESULTS
  Twelve tumors (12%) showed high-frequency MSI (MSI-H). Overall, 43 of the tumors (44%) had at least one LOH event, with most frequent chromosomal losses observed on 10p and 18q (30%, respectively), followed by 5q (21%), 17p (14%), and 17q (12%). Interestingly, overlap was observed between CIN and MSI pathways. Of 43 cancers with LOH events, four (9%) were also MSI-H. It was also found that 48% of cancers without MSI-H had no LOH events identified, comprising a subgroup of tumors that were not representative of either of these two pathways of genomic instability.
  
  
  CONCLUSIONS
  These results suggest that molecular mechanisms of genomic instability are not necessarily independent and may not be fully defined by either the MSI or CIN pathways in sporadic gastric cancers.
authors.affiliation: Health Service Center, Hiroshima University, Higashihiroshima, Japan. tohiyama@hiroshima-u.ac.jp
authors.forename: Toru
authors.initials: T
authors.lastname: Hiyama
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Masaharu
authors.initials: M
authors.lastname: Yoshihara
authors.forename: Shogo
authors.initials: S
authors.lastname: Sasao
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kose
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Shima
authors.forename: Handan
authors.initials: H
authors.lastname: Tuncel
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ueno
authors.forename: Masanori
authors.initials: M
authors.lastname: Ito
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kitadai
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
authors.forename: Ken
authors.initials: K
authors.lastname: Haruma
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D042822:Genomic Instability; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology