DISTAL CHROMOSOME 17Q LOSS IN BARRETTS ESOPHAGEAL AND GASTRIC CARDIA ADENOCARCINOMAS - IMPLICATIONS FOR TUMORIGENESIS

The molecular genetic mechanisms underlying esophageal cancer are poor ly understood. However, a novel gene that may be involved in esophagea l carcinogenesis was recently localized by others to distal 17q by lin kage analysis of kindreds with palmoplantar keratoderma and squamous c ell carcinoma of the esophagus. To help determine whether a distal 17q gene may also be involved in the pathogenesis of primary Barrett's es ophageal and gastric cardia adenocarcinomas, we performed loss of hete rozygosity (LOH) analysis of 21 Barrett's and 18 gastric cardia adenoc arcinomas at loci spanning 17q: cen-BRCA1-SSTR2-D17S2058-D17S929-D1 7S 722-D17S937-D17S802-tel. Over 50% of the Barrett's and cardia adenocar cinomas demonstrated loss of an allele at one or more informative dist al 17q markers. One common overlapping region of loss involved loci ma pped to distal 17q24-proximal 17q25, which tentatively defines a poten tial chromosomal region distal to BRCA1 involved in the pathogenesis o r progression of both types of adenocarcinomas. LOH analysis of DNA fr om matched microdissected sections of Barrett's metaplasia suggested t hat loss of D17S2058 in this region may be an early event in the malig nant transformation of Barrett's metaplasia. No statistically signific ant correlations between 17q LOH and tumor stage or patient survival w ere noted. In summary, LOH mapping of 17q in Barrett's and cardia aden ocarcinomas suggests the existence of at least one putative distal 17q tumor suppressor gene involved in the pathogenesis of these tumors. M el. Carcinog. 22:222-228, 1998. (C) 1998 Wiley-Liss. Inc.