INFREQUENT MUTATIONS AND NO METHYLATION OF CDKN2A (P16 MTS1) AND CDKN2B (P15/MTS2) IN HEPATOCELLULAR-CARCINOMA IN TAIWAN/

CDKN2A (p16(INK4A)/MTS1) and CDKN2B (p15(INK4B)/MTS2) have recently be en shown to be potent inhibitors of the cyclin D/cyclin-dependent kina se-4 complex. Both genes are candidates for the putative tumour suppre ssor genes located at chromosome 9p21 and are frequently inactivated i n many human cancers through homozygous deletion. More recently, anoth er reported pathway of inactivation involves loss of transcription ass ociated with de novo methylation of the 5' CpG island of p16/MTS1 and p15/MTS2 in human cancers. We examined a total of 34 tumours from 30 h epatocellular carcinoma (HCC) patients for deletion, mutation and DNA methylation of these two genes by polymerase chain reaction (PCR) ampl ification, sequence analysis and Southern blot. Homozygous deletions o f P16/MTS1 exon 1 were only identified in 1 of 30 cases (3%). Homozygo us deletions of p15 exon 1 or exon 2 were found in 7 of 30 cases (13%) . Automated sequencing analysis of p16 exon 1 and 2 and p15 exon 1 and 2 failed to demonstrate mutations in either p16 or p15 in any of thes e specimens. No aberrant 5' CpG island hypermethylation of p16 or p15 was found in any of the primary tumours by Southern blot. These data s uggest that the p16/MTS1 gene has a limited role in HCC. However, dele tions of the p15/MTS2 gene are found in 13% HCC and might be involved in a subset of HCC. (C) 1998 Elsevier Science Ltd. All rights reserved .