Mutational study of p16CDKN2/MTS1/INK4A and p57KIP2 genes in hepatocellular carcinoma.

p16 and p15 are representative members of cyclin-dependent kinase inhibitors. Because the selective expression of p57KIP2 in liver, and because p16CDKN2/MTS1/INK4A has been found altered in many primary tumors, we undertook the present study to determine the presence of alterations in these genes in a group of hepatocellular carcinomas (HCC). Seventeen tumor and normal DNA pairs were analyzed by Southern blot, PCR-SSCP and DNA sequencing. Microsatellite markers surrounding the area of the p16 gene was also used. Southern blot analysis did not show allelic losses of the p16 or p57KIP2 genes. In 4 cases, an extra band was observed when hybridizing with the specific p16 cDNA. Overall, 4/17 (24%) cases presented microsatellite alterations at the 9p21-24 region. These results suggest that deletions or point mutations in these genes are not frequent if present at all in HCC, but reveals the existence of microsatellite alterations at the 9p21-24 region in HCC.