Alteration of p16 and p15 genes in human uterine tumours

The roles of the p16 and p15 inhibitor of cyclin-dependent kinase tumour su ppressor genes were examined in human uterine cervical and endometrial canc ers. p16 mRNA, examined by reverse transcription polymerase chain reaction (RT-PCR), was significantly reduced in five of 19 (26%) cervical and four o f 25 (16%) endometrial tumours. Reduced expression of p16 protein, detected by immunohistochemistry, occurred even more frequently, in nine of 33 (27% ) cervical and seven of 37 (19%) endometrial tumours. Hypermethylation of a site within the 5'-CpG island of the p16 gene was detected in only one of 32 (3%) cervical tumours and none of 26 endometrial tumours. Homozygous p16 gene deletion, evaluated by differential PCR analysis, was found in four of 40 (10%) cervical tumours and one of 38 (3%) endometrial tumours. Homozygo us deletion of p15 was found in three of 40 (846) cervical tumours and one of 38 (3%) endometrial tumours. PCR-SSCP (single-strand conformation polymo rphism) analysis detected point mutations in the p16 gene in six (8%) of 78 uterine tumours (four of 40 (10%) cervical tumours and two of 38 (5%) endo metrial tumours). Three were mis-sense mutations, one in codon 74 (CTG-->AT G) and one in codon 129 (ACC-->ATC), both in cervical carcinomas, and the o ther was in codon 127 (GGG-->GAG) in an endometrial carcinoma. There was on e non-sense mutation, in codon 50 (CGA-->TGA), in an endometrial carcinoma. The remaining two were silent somatic cell mutations, both in cervical car cinomas, resulting in no amino acid change. These observations suggest that inactivation of the p16 gene, either by homologous deletion, mutation or l oss of expression, occurs in a subset of uterine tumours.