ALLELOTYPE ANALYSIS OF ESOPHAGEAL SQUAMOUS-CELL CARCINOMA

In previous studies,,ve have shown that allelic loss on chromosome 17p , on which the p53 gene is located, is very frequent, and loss-of-func tion mutations of the p53 gene are closely associated with the tumorig enesis of esophageal cancer. In this study, we performed allelotype an alysis to investigate whether other tumor suppressor genes are also in volved in esophageal cancer. Using 55 poly-morphic DNA markers coverin g every autosomal arm except 13p, 21p, and 22p, restriction fragment l ength polymorphism analysis was performed on 36 esophageal squamous ce ll carcinomas (ESCs) and their adjacent normal tissue samples. Frequen t loss of heterozygosity (LOH) of >30% of the informative cases was ob served on chromosomes 3p (41.1%), 5q (52.6%), 6p (30.4%), 8p (33.3%), 9p (35.7%), 9q (30.8%), 11p (32.4%), 13q (52.7%), 17p (55.2%), 17q (33 .3%), 18q (45.7%), and 19q (30.4%). Among these, LOH on 5q, 13q, 17p, and 18q was previously reported in ESC and is considered to involve th e APC, RB, p53, and DCC genes, respectively. However, our deletion ana lysis of chromosome 18q revealed that the region commonly lost did not include the DCC locus, suggesting that a possible tumor suppressor ge ne on 18q other than the DCC gene is involved in ESC. We screened 60 p rimary ESC tumors and 20 cultured ESC cell lines for the mutation of t he APC gene within a mutation cluster region in exon 15, where the ''h ot spot'' of somatic mutation for colorectal and pancreatic cancers is thought to be. We could not find any mutation despite the high freque ncy of LOH on chromosome 5q. We also analyzed the relationship between the clinicopathological data and the allelic loss and found that LOH on chromosomes 6p and 13q was associated with poor prognosis.