Germline p16(INK4A) mutation and protein dysfunction in a family with inherited melanoma

L. Liu, N. J. Lassam, J. M. Slingerland, D. Bailey, D. Cole, R. Jenkins, D. Hogg

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


The gene encoding the cell cycle inhibitor p16(INK4A) (also known as p16, MTS1, CDKN2 and INK4) has been mapped to human chromosome band 9p21, a region that also contains a putative melanoma susceptibility gene. Although germline mutations in the coding region of the p16(INK4A) gene have been detected in some families with inherited melanoma, many other families show no evidence of such mutations and hence the role of p16(INK4A) in the development of this tumor is still unclear. In this report, we describe a family with inherited melanoma in which a novel mutation in exon 2 of the p16(INK4A) gene segregates with the disease. The mutant gene encodes a protein with an in-frame deletion of two amino acids (Asp96 and Leu97). We show that the mutant protein is functionally abnormal: it is unable to bind cdk4 in vitro and does not inhibit colony formation in tertiary passage rat embryo fibroblasts. Moreover, in a metastatic lesion from one patient the wild type p16(INK4A) allele was deleted and the mutant allele retained. We conclude that family members carrying this germline mutation in the p16(INK4A) gene are predisposed to melanoma. By extension, these findings implicate the p16(INK4A) gene in the development of some cases of familial melanoma.

Original languageEnglish (US)
Pages (from-to)405-412
Number of pages8
Issue number2
StatePublished - 1995


  • Melanoma
  • cdk inhibitors
  • p16(INK4A)

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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