Friday 12 December 2003
p16 is an inhibitor of cyclin-dependent kinases.
p16INK4 gene encodes a specific inhibitor of cyclin-dependent kinase 4 (CDK4). p16INK4a binds to cyclin D-CDK4 and promotes the inhibitory effects of RB.
Since the CDK4/cyclin D complex propels a cell to go through the G1 check point of the cell cycle, a critical phase of cell division, alteration of the p16INK4 gene could lead a cell to uncontrolled proliferation and malignant transformation.
Mutations of the CDKN2A locus have been found in 20% to 50% of familial melanomas.
Among sporadic tumors, p16INK4a mutations are present in up to 50% of pancreatic adenocarcinomas and squamous cell carcinomas of the esophagus, and have also been detected in bladder, head, and neck tumors and in cholangiocarcinomas.
Mutated alleles of p16INK4a present in these tumors have lost their capacity to block cyclin D-CDK4 activity and to prevent RB phosphorylation during the cell cycle. In some tumors, such as cervical cancer, p16INK4a is frequently inactivated by hypermethylation of the gene, without the presence of a mutation (see discussion of epigenetic changes).
germline mutations in familial atypical multiple mole melanoma (FAMMM) (MIM.155601)
- familial melanoma of the skin in combination with multiple atypical precursor naevi (#17492760#)
germline mutation in increased risk of
- pancreatic adenocarcinoma
- carcinomas of the pharynx and oral cavity
- head and neck or oral squamous cell carcinomas (OSCC)
- multiple head and neck tumors
CDKN2A somatic deletion
- glioblastoma (31%)
- anaplastic oligodendroglioma
- supratentorial primitive neuroectodermal tumors of the central nervous system (#17592618#)
Overexpression of p16 has been observed in cervical intraepithelial lesions and invasive carcinomas associated with high-risk HPV types.
Most endocervical adenocarcinomas contain high-risk human papillomavirus (HPV) DNA (endometrial adenocarcinomas rarely do).
CDKN2A is frequently and differentially methylated in ependymal tumours. (#14636164#)
Distinction of endocervical adenocarcinomas and endometrial adenocarcinomas (#15043304#)
low-grade squamous cervical lesions
p16 and L1 immunohistochemistry can be helpful for estimating the biologic potentiality of low-grade squamous cervical lesions. Particularly in cases in which the grade of the lesion is morphologically difficult to assess, the p16/L1 expression pattern could be useful for planning the clinical management of these women.
RB/E2A pathway (P16(INK4A)-CDK4/6-RB pathway)
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