HOMOZYGOUS DELETIONS OF THE CDKN2 GENE AND LOSS OF HETEROZYGOSITY OF 9P IN PRIMARY HEPATOCELLULAR-CARCINOMA

To elucidate the alterations of CDKN2 in hepatocarcinogenesis, we perf ormed a loss of heterozygosity (LOH) study using eight polymorphic mar kers surrounding the CDKN2 gene and analyzed the homozygous deletions and mutations of the CDKN2 gene in 41 primary hepatocellular carcinoma s (HCCs). Frequent LOH (27.8-44%) was found in the eight loci on chrom osome 9p, however, no intragenic mutations of CDKN2 were observed by P CR-SSCP analysis. Homozygous deletions were detected in 25 of 41 HCCs (61%) by a comparative multiplex PCR. No expression of the CDKN2 prote in was noted in five out of nine available HCCs by Western blot analys is. These results suggest that inactivation of the CDKN2 gene in HCC i s a frequent event in which homozygous deletions are the most common m echanism of CDKN2 inactivation. (C) 1998 Elsevier Science Ireland Ltd.