Novel germline CDKN2A mutation associated with head and neck squamous cell carcinomas and melanomas

Head Neck. 2013 Mar;35(3):E80-4. doi: 10.1002/hed.21911. Epub 2011 Nov 15.


Background: The ability to identify individuals at increased risk of cancer is of immediate clinical relevance. Germline mutations in the CDKN2A locus, encoding the key tumor suppressor proteins p16/INK4A and p14/ARF, are frequently present in kindreds with hereditary cutaneous melanoma but have seldom been reported in families with genetic susceptibility to head and neck squamous cell carcinomas (HNSCC).

Methods: We report the pedigree of a patient with an unusually high incidence of HNSCC and melanomas. CDKN2A mutation analysis was performed with standard capillary sequencing and multiplex ligation-dependent probe amplification.

Results: A previously unreported germline CDKN2A mutation affecting only the p16/INK4A open reading frame, c.106delG (p.Ala36ArgfsX17), was detected in the proband. This mutation causes a premature termination codon.

Conclusions: Our report emphasizes the need to consider germinal CDKN2A mutations in the differential diagnosis of familial HNSCC and the importance of awareness of these tumors in carriers of CDKN2A mutations.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Genes, p16
  • Genetic Testing
  • Germ-Line Mutation*
  • Head and Neck Neoplasms / genetics*
  • Humans
  • Male
  • Melanoma / genetics*
  • Middle Aged
  • Pedigree
  • Squamous Cell Carcinoma of Head and Neck
  • Tumor Suppressor Proteins / genetics*


  • Cyclin-Dependent Kinase Inhibitor p16
  • Tumor Suppressor Proteins