Alterations of the p16INK4A gene in human ovarian cancers.

The p16INK4A gene, which encodes the cell-cycle regulatory protein cyclin-dependent kinase 4 inhibitor, is a putative tumor-suppressor gene. We examined p16 gene alterations in 30 primary ovarian cancers and 11 ovarian cancer cell lines. Five of the primary cancers (16.7%) had lost both p16INK4A genes. In addition, four cancers (13.3%) contained five kinds of missense mutations and a one-base deletion. Three cell lines had homozygous deletions of p16 genes, and one cell line had multiple intragenic mutations. There was also suppressed transcription of the p16 gene in one cell line. Some point mutations occurred in the conserved ankylin consensus region. These observations suggest that p16 is a functional target for ovarian carcinogenesis and that p16 alterations occurred in the primary cancers.