Frequent allele loss from chromosome 16q was recently described for human tumors of the breast, prostate gland and liver, indicating the possible presence of a tumor-suppressor gene on that chromosome arm. In this study, the chromosome 16 allele status of 38 hepatocellular carcinomas in Chinese patients was determined with restriction-fragmentlength polymorphism analysis. Tumor-specific allele loss was detected in 14 (74%) of 19 patients informative for 16p markers and in 22 (85%) of 26 patients informative for 16q markers. Quantitative densitometric analysis revealed reduction to hemizygosity of the E-cadherin cell adhesion gene (localized to 16q22.1) in 18 (64%) of the 28 patients for whom quantitative data were available. Reduced expression of E-cadherin has been associated with invasion and metastasis in several human cell lines and primary tumors, and our results suggest that one mechanism of reduced E-cadherin expression is the loss of one copy of the E-cadherin gene. (HEPATOLOGY 1993;18:757-762.)
The development of HCC is believed to result from the accumulation of multiple genetic changes, and risk factors such as chronic infection with HBV and exposure to dietary aflatoxins are clearly related to the high incidence of HCC in certain parts of the world (1-5). Recent restriction-fragment-length polymorphism (RFLP) studies of human liver tumors have revealed significant allele losses from regions of chromosomes 4 (6, 7), 5q (8), l l p (8, 9), 13q (9), 16q (6, 8, 10) and 17p (€411,121. These observations have been interpreted to suggest an important role for the inactivation of tumorsuppressor-like genes that reside in those specific chromosomal regions. The presence of inactivation mutations in tumor-suppressor gene p53 (located on chromosome 17p) is well-documented for HCCs from certain regions of China (12-14) and southern Africa (15), but the genes that may serve as potential targets for the selective deletions on chromosomes 4, 5q, l l p ,