Genetic alterations in the ink4a/arf locus: effects on melanoma development and progression

Zizhen Ming, Su Yin Lim, Helen Rizos*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

19 Citations (Scopus)
27 Downloads (Pure)


Genetic alterations in the INK4a/ARF (or CDKN2A) locus have been reported in many cancer types, including melanoma; head and neck squamous cell carcinomas; lung, breast, and pancreatic cancers. In melanoma, loss of function CDKN2A alterations have been identified in approximately 50% of primary melanomas, in over 75% of metastatic melanomas, and in the germline of 40% of families with a predisposition to cutaneous melanoma. The CDKN2A locus encodes two critical tumor suppressor proteins, the cyclin‐dependent kinase inhibitor p16INK4a and the p53 regulator p14ARF. The majority of CDKN2A alterations in melanoma selectively target p16INK4a or affect the coding sequence of both p16INK4a and p14ARF. There is also a subset of less common somatic and germline INK4a/ARF alterations that affect p14ARF, while not altering the syntenic p16INK4a coding regions. In this review, we describe the frequency and types of somatic alterations affecting the CDKN2A locus in melanoma and germline CDKN2A alterations in familial melanoma, and their functional consequences in melanoma development. We discuss the clinical implications of CDKN2A inactivating alterations and their influence on treatment response and resistance.

Original languageEnglish
Article number1447
Pages (from-to)1-17
Number of pages17
Issue number10
Publication statusPublished - 1 Oct 2020

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • CDKN2A
  • INK4a/ARF
  • Melanoma
  • P14
  • P16
  • Tumor suppressor proteins


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