Features associated with germline CDKN2A mutations: A GenoMEL study of melanoma-prone families from three continents

Alisa M. Goldstein, May Chan, Mark Harland, Nicholas K. Hayward, Florence Demenais, D. Timothy Bishop, Esther Azizi, Wilma Bergman, Giovanna Bianchi-Scarra, William Bruno, Donato Calista, Lisa A. Cannon Albright, Valerie Chaudru, Agnes Chompret, Francisco Cuellar, David E. Elder, Paola Ghiorzo, Elizabeth M. Gillanders, Nelleke A. Gruis, Johan HanssonDavid Hogg, Elizabeth A. Holland, Peter A. Kanetsky, Richard F. Kefford, Maria Teresa Landi, Julie Lang, Sancy A. Leachman, Rona M. MacKie, Veronica Magnusson, Graham J. Mann, Julia Newton Bishop, Jane M. Palmer, Susana Puig, Joan A. Puig-Butille, Mitchell Stark, Hensin Tsao, Margaret A. Tucker, Linda Whitaker, Emanuel Yakobson, Christian Ingvar, Ake Borg, Johan Westerdahl, Anna Masback, Hakan Olsson, Josep Malvehy, Celia Badenas, Remedios Cervera, Rosa Martí, Joan Brunet-Vidal, Guang Yang, Nicholas Martin, David Whiteman, Adele Green, Joanne Aitken, Paola Minghetti, Michela Mantelli, Lorenza Pastorino, Sabina Nasti, Sara Gargiulo, Sara Gliori, Sushila Mistry, Juliette Randerson-Moor, Femke A. De Snoo, Jeanet A.C. Ter Huurne, Jasper Van Der Rhee, Leny Van Mourik, Frans Van Nieuwpoort, Clasine Van Der Drift, Brigitte Bressac-De Paillerets, Marie Francoise Avril, F. Grange, B. Sassolas, F. Boitier, J. Chevrant-Breton, C. Lasset, C. Dugast, P. Vabres, Arupa Ganguly, Michael Ming, Patricia Van Belle, Anton Platz, Suzanne Egyhazi, Rainer Tuominen, Diana Linden, Helen Schmid, Alon Scope, Felix Pavlotsky, Eitan Friedman, Mark Eliason

Research output: Contribution to journalArticlepeer-review

302 Scopus citations


Background: The major factors individually reported to be associated with an increased frequency of CDKN2A mutations are increased number of patients with melanoma in a family, early age at melanoma diagnosis, and family members with multiple primary melanomas (MPM) or pancreatic cancer. Methods: These four features were examined in 385 families with ≥3 patients with melanoma pooled by 17 GenoMEL groups, and these attributes were compared across continents. Results: Overall, 39% of families had CDKN2A mutations ranging from 20% (32/162) in Australia to 45% (29/65) in North America to 57% (89/157) in Europe. All four features in each group, except pancreatic cancer in Australia (p = 0.38), individually showed significant associations with CDKN2A mutations, but the effects varied widely across continents. Multivariate examination also showed different predictors of mutation risk across continents. In Australian families, ≥2 patients with MPM, median age at melanoma diagnosis ≤40 years and ≥6 patients with melanoma in a family jointly predicted the mutation risk. In European families, all four factors concurrently predicted the risk, but with less stringent criteria than in Australia. In North American families, only ≥1 patient with MPM and age at diagnosis ≤40 years simultaneously predicted the mutation risk. Conclusions: The variation in CDKN2A mutations for the four features across continents is consistent with the lower melanoma incidence rates in Europe and higher rates of sporadic melanoma in Australia. The lack of a pancreatic cancer-CDKN2A mutation relationship in Australia probably reflects the divergent spectrum of mutations in families from Australia versus those from North America and Europe. GenoMEL is exploring candidate host, genetic and/or environmental risk factors to better understand the variation observed.

Original languageEnglish (US)
Pages (from-to)99-106
Number of pages8
JournalJournal of medical genetics
Issue number2
StatePublished - Feb 2007
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Features associated with germline CDKN2A mutations: A GenoMEL study of melanoma-prone families from three continents'. Together they form a unique fingerprint.

Cite this