Substantial reduction of the gastric carcinoma critical region at 6q16.3-q23.1

Deletions of the long arm of chromosome 6 are a common event in gastric car cinomas. In a previous study, deletion mapping of 6q identified two smalles t regions of overlap (SROs) of heterozygous deletions: one interstitial, sp anning 12-16 cM, bordered by D6S268 (6q16.3-q21) and ARGI (6q22.3-q23.1), a nd one distal to IFNGRI (6q23-q24), spanning more than 30 cM. Loss of heter ozygosity (LOH) of the interstitial SRO was detected in 50% of informative tumors. We analyzed 60 primary gastric tumors with 19 highly polymorphic ma rkers from 6q16.3-q23.3 to delimit the interstitial SRO further. Of the 50 tumors that were informative for at least one locus, 18 (36%) showed alleli c imbalance (Al), The overlap of these cases allowed us to define an SRO of approximately 3 Mb flanked by D6S278 and D6S404. Al or LOH of this region occurs in all histologic types of gastric carcinoma and in early stages of development, indicating that loss of a gene from this region of 6q is a cru cial step in a main route of gastric carcinogenesis. For cases with retenti on of 6q, alternative routes of gastric carcinogenesis may exist. (C) 1999 Wiley-Liss, Inc.