Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families

Research output: Contribution to journalArticle


Germline mutations in CDKN2A are frequently identified among melanoma kindreds and are associated with increased atypical nevus counts. However, a clear relationship between pathogenic CDKN2A mutation carriage and other nevus phenotypes including counts of common acquired nevi has not yet been established. Using data from GenoMEL, we investigated the relationships between CDKN2A mutation carriage and 2-mm, 5-mm, and atypical nevus counts among blood-related members of melanoma families. Compared with individuals without a pathogenic mutation, those who carried one had an overall higher prevalence of atypical (odds ratio = 1.64; 95% confidence interval = 1.18–2.28) nevi but not 2-mm nevi (odds ratio = 1.06; 95% confidence interval = 0.92–1.21) or 5-mm nevi (odds ratio = 1.26; 95% confidence interval = 0.94–1.70). Stratification by case status showed more pronounced positive associations among non-case family members, who were nearly three times (odds ratio = 2.91; 95% confidence interval = 1.75–4.82) as likely to exhibit nevus counts at or above the median in all three nevus categories simultaneously when harboring a pathogenic mutation (vs. not harboring one). Our results support the hypothesis that unidentified nevogenic genes are co-inherited with CDKN2A and may influence carcinogenesis.


  • Nicholas J. Taylor
  • Nandita Mitra
  • Alisa M. Goldstein
  • Margaret A. Tucker
  • Marie Françoise Avril
  • Esther Azizi
  • Wilma Bergman
  • D. Timothy Bishop
  • Brigitte Bressac-de Paillerets
  • William Bruno
  • Donato Calista
  • Lisa A. Cannon-Albright
  • Francisco Cuellar
  • Anne E. Cust
  • Florence Demenais
  • David E. Elder
  • Anne Marie Gerdes
  • Paola Ghiorzo
  • Thais C. Grazziotin
  • Johan Hansson
  • Mark Harland
  • Nicholas K. Hayward
  • Marko Hocevar
  • Veronica Höiom
  • Christian Ingvar
  • Maria Teresa Landi
  • Gilles Landman
  • Alejandra Larre-Borges
  • Sancy A. Leachman
  • Graham J. Mann
  • Eduardo Nagore
  • Håkan Olsson
  • Jane M. Palmer
  • Barbara Perić
  • Dace Pjanova
  • Antonia Pritchard
  • Susana Puig
  • Nienke van der Stoep
  • Karin A.W. Wadt
  • Linda Whitaker
  • Xiaohong R. Yang
  • Julia A. Newton Bishop
  • Nelleke A. Gruis
  • Peter A. Kanetsky
  • GenoMEL Study Group
External organisations
  • University of Pennsylvania
  • National Cancer Institute, USA
  • Paris Descartes University
  • Tel-Aviv University
  • Leiden University Medical Centre
  • St James's University Hospital
  • University of Paris-Saclay
  • University of Genoa
  • Hospital Clínic of Barcelona
  • University of Sydney
  • Melanoma Institute Australia
  • Paris Diderot University
  • Copenhagen University Hospital
  • Federal University of Health Sciences of Porto Alegre
  • QIMR Berghofer Medical Research Institute
  • Institute of Oncology, Ljubljana
  • University of the Republic
  • Oregon Health & Science University
  • Instituto Valenciano de Oncologia
  • Latvian Biomedical Research and Study Centre
  • H. Lee Moffitt Cancer Center & Research Institute
  • Texas A and M University
  • University of Leeds
  • Ospedale Policlinico San Martino
  • Maurizio Bufalini Hospital
  • University of Utah
  • Biomedical Network on Rare Diseases (CIBERER)
  • Karolinska Institutet
  • Federal University of São Paulo
  • Cochin Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Dermatology and Venereal Diseases
  • Medical Genetics
Original languageEnglish
Pages (from-to)2606-2612
Number of pages7
JournalJournal of Investigative Dermatology
Issue number12
Publication statusPublished - 2017 Dec 1
Publication categoryResearch