title: A novel region of amplification at 11p12-13 in gastric cancer, revealed by representational difference analysis, is associated with overexpression of CD44v6, especially in early-onset gastric carcinomas.
abstract: Diffuse-type gastric carcinomas (GCs) are often difficult to characterize because of contamination of tumor samples by surrounding normal tissue. As such, information regarding chromosomal aberrations in this subtype of GCs is limited. In this study, we used representational difference analysis to pinpoint genomic amplifications occurring in diffuse-type GCs. We found nine differential products from two novel regions of amplification in two tumors: one product mapped to 19p13.1 and eight mapped to a 1.8-Mb region in chromosomal segment 11p12-13. These amplifications were confirmed using Southern blot analysis and occurred in 3/16 and 6/15 diffuse-type GCs, respectively. CD44, a well characterized cellular adhesion molecule involved in several human malignancies, is encoded by a gene located within 200 kb of the 11p12-13 amplification fragments. We confirmed that overexpression of isoform CD44v6 was correlated with amplification at 11p12-13 in 11/12 diffuse-type GCs. Since diffuse-type GCs occur more frequently in early-onset gastric carcinomas (EOGCs, presented at 45 years of age or younger) than in "conventional" GCs, and the tumors carrying the original amplifications were EOGCs, we investigated overexpression of CD44v6 in 107 EOGCs and 88 conventional GCs using tissue microarrays. We found frequent CD44v6 overexpression in both tumor groups (76% and 57% respectively) and, interestingly, significantly more cases with overexpression of CD44v6 in EOGCs than in conventional GCs (P = 0.005), irrespective of histology. These findings provide further evidence for both the relevance of CD44 in GC and for distinct molecular characteristics of EOGCs when compared with those of GCs occurring at a later age.
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: G Johan A
authors.initials: GJ
authors.lastname: Offerhaus
authors.forename: Marian A J
authors.initials: MA
authors.lastname: Weterman
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D017668:Age of Onset; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: C112697:CD44v6 antigen; D006023:Glycoproteins; D018960:Hyaluronan Receptors