Hepatocellular carcinoma (HCC) is one of the most common cancers in Asia and Africa. HCCs from the Qidong region of China are frequently mutated in the tumor suppressor gene p53 and in a region near the TAT locus on chromosome 16. We are extending previous studies by examining a larger set of samples from Qidong and Beijing, and by concentrating on markers specific to the long (or 'q') arm of chromosome 16. Our long-term goal is to identify and characterize new tumor suppressor genes on chromosome 16. Restriction fragment length polymorphism (RFLP) studies of the tumor suppressor gene p53 of chromosome 17 have revealed extensive chromosomal aberrations (CA). These include both loss of heterozygosity (LOH) and small (200-600 basepair) deletions. To date, out of 50 samples examined, 41 were informative (that is they were heterozygous for at least one RFLP site) and of these, 34 (83%) showed some form of chromosomal aberration, either LOH or deletion for p53. RFLP studies of the TAT locus of chromosome 16 have been less informative owing to a lower incidence of polymorphism than was found for p53. Out of 15 informative samples, 11 displayed LOH (73%). In total, 45 out of 51 (88%) samples were informative for at least one combination of probe and restric-tion enzyme for either p53 or TAT, and 39 (87%) of these demonstrated consistent, quantitative evidence for CA. The frequencies with which CA arose in either the p53 locus or the TAT locus appear to be independent of one another (Chi-square test). In the following year, we plan to intensify the analysis of the 'q' arm of chromosome 16 in order to narrow the regions of overlapping CA. Because of the low frequency of informative samples for the TAT locus, this study is proceeding using quantitative Southern blotting to detect deletions in homozygous loci. Other techniques we are investigating include polymerasechain reaction (PCR) amplification of polymorphic microsatellites (again to search for regions of LOH) and scanning larger sections of the chromosome using long-range PCR.
