title: The gene-reduction effect of chromosomal losses detected in gastric cancers.
abstract: BACKGROUND
  The level of loss of heterozygosity (LOH) that reduces a gene dose and exerts a cell-adverse effect is known to be a parameter for the genetic staging of gastric cancers. This study investigated if the cell-adverse effect induced with the gene reduction was a rate-limiting factor for the LOH events in two distinct histologic types of gastric cancers, the diffuse- and intestinal-types.
  
  
  METHODS
  The pathologic specimens obtained from 145 gastric cancer patients were examined for the level of LOH using 40 microsatellite markers on eight cancer-associated chromosomes (3p, 4p, 5q, 8p, 9p, 13q, 17p and 18q).
  
  
  RESULTS
  Most of the cancer-associated chromosomes were found to belong to the gene-poor chromosomes and to contain a few stomach-specific genes that were highly expressed. A baseline-level LOH involving one or no chromosome was frequent in diffuse-type gastric cancers. The chromosome 17 containing a relatively high density of genes was commonly lost in intestinal-type cancers but not in diffuse-type cancers. A high-level LOH involving four or more chromosomes tended to be frequent in the gastric cancers with intestinal and mixed differentiation. Disease relapse was common for gastric cancers with high-level LOH through both the hematogenous (38%) and non-hematogenous (36%) routes, and for the baseline-level LOH cases through the non-hematogenous route (67%).
  
  
  CONCLUSIONS
  The cell-adverse effect of gene reduction is more tolerated in intestinal-type gastric cancers than in diffuse-type cancers, and the loss of high-dose genes is associated with hematogenous metastasis.
authors.affiliation: Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seung-Jin
authors.initials: SJ
authors.lastname: Hong
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Jeon
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Oh
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Seo
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Choi
authors.forename: Mun-Gan
authors.initials: MG
authors.lastname: Rhyu
mesh_terms: D001706:Biopsy; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm