ACCUMULATION OF GENETIC ALTERATIONS DURING ESOPHAGEAL CARCINOGENESIS

Using polymerase chain reaction amplification of microsatellite region s in DNA from 11 epithelial dysplasias of the esophagus and 21 early s quamous cell carcinomas, we were able to detect frequent lass of heter ozygosity (LOH) on chromosomes 3p21.3 and 9q31 even in low-grade dyspl asias. In contrast, we observed frequent LOHs on chromosomes 9p22 and 17p13 (TP53 locus) only in high-grade dysplasias and carcinomas, but n ot in any low-grade dysplasias. Analysis of LOH at the same four chrom osomal regions in DNA of five additional minimal carcinomas and accomp anying dysplastic lesions revealed loss of alleles at the loci on 3p21 .3 and 9q31 throughout various degrees of dysplasia and carcinoma; aga in, LOHs on 9p22 and 17p13 occurred only in high-grade dysplasia and c arcinoma in situ. Our results indicated that inactivation of putative tumor suppressor genes on 3p21.3 and 9q31 may be early genetic events during esophageal carcinogenesis, and that additional genetic alterati ons on 9p22 and 17p13 probably play roles in progression.