ALLELOTYPE ANALYSIS OF ESOPHAGEAL ADENOCARCINOMA - LOSS OF HETEROZYGOSITY OCCURS AT MULTIPLE SITES

Deletions of tumour-suppressor genes can be detected by loss of hetero zygosity (LOH) studies, which were performed on 23 cases of adenocarci noma of the oesophagus, using 120 microsatellite primers covering ail non-acrocentric autosomal chromosome arms. The chromosomal arms most f requently demonstrating LOH were 3p (64% of tumours), 5q (45%), 9p (52 %), 11p (61%), 13q (50%), 17p (96%), 17q (55%) and 18q (70%). LOH on 3 p, 9p, 13q, 17p and 18q occurred mainly within the loci of the VHL, CD KN2, Rb, TP53 and DCC tumour-suppressor genes respectively. LOH on 5q occurred at the sites of the MSH3 mismatch repair gene and the APC tum our-suppressor gene. 11p15.5 and 17q25-qter represented areas of great est LOH on chromosomes 11p and 17q, and are putative sites of novel tu mour-suppressor genes. LOH on 9p was significantly associated with LOH on 59, and tumours demonstrating LOH at both the CDKN2 (9p21) and MSH 3 (5q11-q12) genes had a significantly higher fractional allele loss t han those retaining heterozygosity at these sites. Six of nine carcino mas displaying microsatellite alterations also demonstrated LOH at CDK N2, which may be associated with widespread genomic instability, Overa ll, there are nine sites of LOH associated with oesophageal adenocarci noma.