CDKN2A germline mutations in individuals with cutaneous malignant melanoma Journal Article


Authors: Orlow, I.; Begg, C. B.; Cotignola, J.; Roy, P.; Hummer, A. J.; Clas, B. A.; Mujumdar, U.; Canchola, R.; Armstrong, B. K.; Kricker, A.; Marrett, L. D.; Millikan, R. C.; Gruber, S. B.; Anton-Culver, H.; Zanetti, R.; Gallagher, R. P.; Dwyer, T.; Rebbeck, T. R.; Kanetsky, P. A.; Wilcox, H.; Busam, K.; From, L.; Berwick, M.
Article Title: CDKN2A germline mutations in individuals with cutaneous malignant melanoma
Abstract: Cyclin-dependent kinase inhibitor type 2A (CDKN2A) has been identified as a major melanoma susceptibility gene based on the presence of germline mutations in high-risk melanoma families. In this study, we sought to identify and characterize the spectrum of CDKN2A mutations affecting p16 inhibitor of cyclin-dependent kinase type 4 (INK4a) in individuals with melanoma using a population-based study design. DNA samples from 1189 individuals with incident multiple primary melanoma (MPM) and 2424 with incident single primary melanoma unselected for family history of melanoma were available for screening of CDKN2A (p16INK4a) mutations. Variants were classified for functional impact based on intragenic position, existing functional data, sequence, and structural analysis. The impact of individual mutations and functional groupings was assessed by comparing frequencies in cases of MPM versus cases with a single first primary melanoma, and by comparing the reported incidence rates in first-degree relatives. Our results show that mutations occur infrequently in these high-risk groups, and that they occur mainly in exons 1α and 2. Rare coding variants with putative functional impact are observed to increase substantially the risk of melanoma. With the exception of the variant in position -34 of CDKN2A of known functional consequence, the remaining rare variants in the non-coding region have no apparent impact on risk. © 2007 The Society for Investigative Dermatology.
Keywords: gene mutation; gene sequence; exon; exons; genetic predisposition to disease; melanoma; skin neoplasms; incidence; genetic variability; risk factors; risk assessment; population research; dna; screening; dna, neoplasm; dna sequence; high risk population; cyclin-dependent kinase inhibitor p16; cyclin dependent kinase inhibitor; genetic screening; genetic code; germ-line mutation; relative
Journal Title: Journal of Investigative Dermatology
Volume: 127
Issue: 5
ISSN: 0022-202X
Publisher: Nature Publishing Group  
Date Published: 2007-05-01
Start Page: 1234
End Page: 1243
Language: English
DOI: 10.1038/sj.jid.5700689
PUBMED: 17218939
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 17" - "Export Date: 17 November 2011" - "CODEN: JIDEA" - "Source: Scopus"
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MSK Authors
  1. Amanda J Hummer
    60 Hummer
  2. Colin B Begg
    239 Begg
  3. Marianne Berwick
    119 Berwick
  4. Irene Orlow
    192 Orlow
  5. Klaus J Busam
    540 Busam
  6. Pampa Roy
    32 Roy
  7. Brian Clas
    9 Clas