A melanoma-associated germline mutation in exon 1β inactivates p14ARF

Helen Rizos*, Susana Puig, Cèlia Badenas, Josep Malvehy, Artur P. Darmanian, Loli Jiménez, Montserrat Milà, Richard F. Kefford

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

158 Citations (Scopus)


The INK4a/ARF locus encodes the cyclin dependent kinase inhibitor, p16INK4a and the p53 activator, p14ARF. These two proteins have an independent first exon (exon 1α and exon 1β, respectively) but share exons 2 and 3 and are translated in different reading frames. Germline mutations in this locus are associated with melanoma susceptibility in 20-40% of multiple case melanoma families. Although most of these mutations specifically inactivate p16INK4a, more than 40% of the INK4a/ARF alterations located in exon 2, affect both p16INK4a and p14ARF. We now report a 16 base pair exon 1β germline insertion specifically altering p14ARF, but not p16INK4a, in an individual with multiple primary melanomas. This mutant p14ARF, 60ins16, was restricted to the cytoplasm, did not stabilize p53 and was unable to arrest the growth of a p53 expressing melanoma cell line. This is the first example of an exon 1β mutation that inactivates pl4ARF, and thus implicates a role for this turnout suppressor in melanoma predisposition.

Original languageEnglish
Pages (from-to)5543-5547
Number of pages5
Issue number39
Publication statusPublished - 6 Sept 2001
Externally publishedYes


  • Germline mutation
  • Melanoma
  • P14ARF
  • P16


Dive into the research topics of 'A melanoma-associated germline mutation in exon 1β inactivates p14ARF'. Together they form a unique fingerprint.

Cite this