Semi-automated quantitative method for detecting the loss of heterozygosity at chromosome 4 in hepatocellular carcinoma

Objectives - Chromosomal deletions are the most frequent genetic alteration s observed in hepatocellular carcinoma. Loss of heterozygosity on chromosom e 4q has been observed in 40% of hepatocellular carcinomas suggesting the p resence of a tumor suppressor gene which has not yet been identified. Methodology - We developed a semi-automated quantitative genotyping method which allowed us to characterize 119 hepatocellular carcinomas with 22 fluo rescent microsatellite markers distributed on chromosome 4q. Results - 4q loss was observed in 40% of cases. Among these deletions, 19 c ases of partial or interstitial loss made it possible to define two common minimal regions of deletion of 25.1 and 37.6 centimorgans localized between markers D4S414 and D4S430 and between markers D4S3033 and D4S408, respecti vely. Conclusion - This work represents the first step towards the identification and characterization of new genes involved in hepatic carcinogenesis.