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Home > A. Molecular pathology > CDKN2A


MIM.600160 9p21

Friday 12 December 2003


Definition: 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.


- CDKN2A FISH and BAP1 IHC in malignant mesothelioma


- mutations CDKN2A
- deletions CDKN2A
- inhibition CDKN2A
- overexpression CDKN2A

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 :

- CDKN2A somatic deletion

- Overexpression of CDKN2A / p16

  • in cervical intraepithelial lesions and invasive carcinomas associated with high-risk HPV types.

By tumors

- cervical intraepithelial lesions and cervical SCC

  • Overexpression of CDKN2A / p16 in cervical intraepithelial lesions and invasive squamous cell carcinomas (SCCs) associated with high-risk HPV types.

- Most endocervical adenocarcinomas contain high-risk human papillomavirus (HPV) DNA (endometrial adenocarcinomas rarely do).


- CDKN2A FISH and BAP1 IHC in malignant mesothelioma

Some mutations

- CDKN2A-M53I (17171691)


- CDKN2A is frequently and differentially methylated in ependymal tumors . (14636164)

Diagnosis use

- See p16

See also

- ARF (p14ARF)
- RB/E2A pathway (P16(INK4A)-CDK4/6-RB pathway)




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- Weitzman JB. p16(Ink4a) and p19(Arf): terrible twins. Trends Mol Med. 2001 Nov;7(11):489. PMID: 11689318


- p16 FISH deletion in surface epithelial mesothelial proliferations is predictive of underlying invasive mesothelioma. Hwang H, Tse C, Rodriguez S, Gown A, Churg A. Am J Surg Pathol. 2014 May;38(5):681-8. doi : 10.1097/PAS.0000000000000176 PMID: 24503757

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