Mutations, methylation and expression of CDKN2a/p16 gene in colorectal cancer and normal colonic mucosa.

The status of CDKN2a gene, coding for p16 and p19ARF proteins, was examined in 55 colorectal cancers. Polymerase chain reaction (PCR), single stranded conformational polymorphism and sequencing revealed 1 case of CDKN2a mutation. Methylation-specific PCR detected p16 locus methylation in 37 (73%) of 51 normal samples and 29 (53%) of 55 cancers (P=0.035). p16 transcript absence (assessed by reverse transcription-polymerase chain reaction) was noted in 10 (45%) of 22 normal samples and four (14%) of 29 cancers (P=0.012) and correlated with gene methylation (P=0.036). The decreasing frequency of p16 silencing in cancer comparing to normal mucosa does not support the postulated role of p16 in colorectal carcinogenesis.