title: Exclusion of RUNX3 as a tumour-suppressor gene in early-onset gastric carcinomas.
abstract: Recent studies claim a critical role for RUNX3 in gastric epithelial homeostasis. However, conflicting results exist regarding RUNX3 expression in the stomach and its potential role as a tumour-suppressor gene (TSG) in gastric carcinogenesis. Our aim was to evaluate the role of RUNX3 in early-onset gastric carcinomas (EOGCs). We analysed 41 EOGCs for RUNX3 aberrations using loss of heterozygosity (LOH), fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) analyses. LOH of markers flanking RUNX3 was relatively common, indicating that loss of the gene may play a role in gastric carcinogenesis. However, FISH analysis of selected cases and a panel of 14 gastric carcinoma-derived cell lines showed widespread presence of multiple copies of centromere 1. While RUNX3 copy numbers were generally equal to or fewer than those of centromere 1, at least two copies were present in almost all cells analysed. Accordingly, a subpopulation of tumour cells in 12/37 cases showed RUNX3 protein expression. However, expression was not detected in the adjacent nontumorous mucosa of any case. Together, these observations indicate that chromosome 1 aberrations occur frequently in EOGCs and are reflected in the LOH and IHC patterns found. Our findings refute a role for RUNX3 as a TSG in EOGCs.
authors.affiliation: Department of Pathology, Academisch Medisch Centrum, Amsterdam, The Netherlands. r.p.carvalho@amc.uva.nl
authors.forename: Ralph
authors.initials: R
authors.lastname: Carvalho
authors.forename: Anya N A
authors.initials: AN
authors.lastname: Milne
authors.forename: Mirjam
authors.initials: M
authors.lastname: Polak
authors.forename: Willem E
authors.initials: WE
authors.lastname: Corver
authors.forename: G Johan A
authors.initials: GJ
authors.lastname: Offerhaus
authors.forename: Marian A J
authors.initials: MA
authors.lastname: Weterman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D009363:Neoplasm Proteins; C493729:Runx3 protein, human; D025521:Tumor Suppressor Proteins