LOSS OF HETEROZYGOSITY ON CHROMOSOME-9 AND P16 (MTS1, CDKN2) GENE-MUTATIONS IN ESOPHAGEAL CANCERS

Loss of heterozygosity on chromosome 9 has been reported in a variety of human cancers. The cyclin-dependent kinase inhibitor p16 gene, mapp ed on chromosome 9p21, is presumed to be the tumor-suppressor gene loc alized in this chromosome. The aim of our study was to determine, in 2 6 Barrett's adenocarcinomas and 20 squamous-cell carcinomas of the eso phagus, the prevalence of loss of heterozygosity on chromosome 9 by ty ping of microsatellite loci and mutation of p16 by direct sequencing o f exons 1 and 2. Allelic losses were found in 69% of adenocarcinomas, but only a microdeletion in exon 1 of p16 occurred in 1 tumor. Among s quamous-cell carcinomas, 65% had allelic losses and 5 tumors were muta ted on the p16 gene (1 deletion, 3 nucleotide substitutions and 1 inse rtion). The relatively low rate of p16 mutation observed here coupled with the high frequency of loss of heterozygosity on chromosome 9 sugg ests that one or several tumor-suppressor gene(s) distinct from p16 ma y be the target(s) of allelic deletion in most esophageal cancers or t hat p16 is inactivated in another way. (C) 1997 Wiley-Liss, Inc.