Allelic loss on chromosomes 4q and 16q in hepatocellular carcinoma: association with elevated alpha-fetoprotein production.

BACKGROUND & AIMS: In human hepatocellular carcinoma, restriction fragment length polymorphism analysis has shown frequent allelic loss on chromosomes 4q and 16q. To better define the commonly affected region for further positional cloning of the putative tumor-suppressor genes contained in these two chromosome arms, microsatellite polymorphism analysis was conducted to analyze extensively the allelic loss on both chromosome loci.

METHODS

DNA from 42 pairs of large hepatocellular carcinoma (> 5 cm) and corresponding nonneoplastic liver tissues were prepared. Allelic loss on chromosome 4q and 16q was investigated by 13 or 12 sets of microsatellite polymorphic markers.

RESULTS

The frequency of allelic loss on chromosome 16q was 70%, and the common region was mapped to 16q22-23. An even higher frequency (77%) was found on chromosome 4q with the common region mapped to 4q12-23. The allelic loss of chromosome 4q was significantly associated with hepatocellular carcinoma of elevated serum alpha-fetoprotein but not with those of normal level (91% vs. 30%; Fisher's Exact Test, two-tailed P = 1.12 x 10(-4)).

CONCLUSIONS

The results form the basis for further positional cloning of putative tumor-suppressor genes on chromosome 4q and 16q. Moreover, the one on chromosome 4q might shed light on the mechanism of alpha-fetoprotein expression in hepatocellular carcinoma.