This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hashemi, J. Articles by Hansson, J. Search for Related Content PubMed PubMed Citation Articles by Hashemi, J. Articles by Hansson, J.

CDKN2A Germ-line Mutations in Individuals with Multiple Cutaneous Melanomas¹

Radiumhemmet, Department of Oncology-Pathology, Karolinska Hospital, S-171 76 Stockholm, Sweden [J. Has., A. P., T. U., U. R., J. Han.], and Department of Oncology, Sahlgrenska University Hospital, S-413 45 Gothenburg, Sweden [U. S.]

Germ-line CDKN2A mutations are present in some kindreds with hereditary cutaneous melanoma, and in Sweden a founder mutation with an extra arginine in codon 113 (113insR) has been identified. We screened 80 individuals with at least two primary cutaneous melanomas, who were identified mainly by a search of a regional cancer registry, for germ-line CDKN2A mutations. In nine patients, CDKN2A alterations that may contribute to melanoma predisposition were detected. In six individuals with a family history of melanoma, the 113insR founder mutation was present. One patient, who also had a family history of melanoma, had a 24-bp deletion that included codons 62–69. An in vitro binding assay established that the resulting mutant p16 protein was unable to bind cyclin-dependent kinase 4 and cyclin-dependent kinase 6. Two patients without a family history of melanoma had CDKN2A alterations: (a) one had a mutation in the 5' noncoding sequence (-14C/T); and (b) the other had an insertion of an extra T in codon 28, which results in a stop signal in codon 43. The median age at diagnosis of the first melanoma was significantly lower, the number of primary melanomas was significantly higher, and the presence of a family history of melanoma was significantly more common in patients with CDKN2A mutations than in those without germ-line mutations. The proportion of CDKN2A mutation carriers was significantly higher among patients treated for three or more primary melanomas compared with those with two tumors only. We conclude that mutation screening of individuals with multiple primary melanomas is a useful strategy to identify new melanoma kindreds with CDKN2A germ-line mutations.

This article has been cited by other articles:

				M. J. Eliason, C. B. Hansen, M. Hart, P. Porter-Gill, W. Chen, R. A. Sturm, G. Bowen, S. R. Florell, R. M. Harris, L. A. Cannon-Albright, et al. Multiple Primary Melanomas in a CDKN2A Mutation Carrier Exposed to Ionizing Radiation Arch Dermatol, November 1, 2007; 143(11): 1409 - 1412. [Abstract] [Full Text] [PDF]

				S. Puig, J. Malvehy, C. Badenas, A. Ruiz, D. Jimenez, F. Cuellar, A. Azon, U. Gonzalez, T. Castel, A. Campoy, et al. Role of the CDKN2A Locus in Patients With Multiple Primary Melanomas J. Clin. Oncol., May 1, 2005; 23(13): 3043 - 3051. [Abstract] [Full Text] [PDF]

				T. Debniak, R. J. Scott, T. Huzarski, T. Byrski, A. Rozmiarek, B. Debniak, E. Zaluga, R. Maleszka, J. Kladny, B. Gorski, et al. CDKN2A Common Variants and Their Association with Melanoma Risk: A Population-Based Study Cancer Res., February 1, 2005; 65(3): 835 - 839. [Abstract] [Full Text] [PDF]

				J. Huang, M. El-Gamil, M. E. Dudley, Y. F. Li, S. A. Rosenberg, and P. F. Robbins T Cells Associated with Tumor Regression Recognize Frameshifted Products of the CDKN2A Tumor Suppressor Gene Locus and a Mutated HLA Class I Gene Product J. Immunol., May 15, 2004; 172(10): 6057 - 6064. [Abstract] [Full Text] [PDF]

				M. Eskandarpour, J. Hashemi, L. Kanter, U. Ringborg, A. Platz, and J. Hansson Frequency of UV-Inducible NRAS Mutations in Melanomas of Patients With Germline CDKN2A Mutations J Natl Cancer Inst, June 4, 2003; 95(11): 790 - 798. [Abstract] [Full Text] [PDF]

				H. T. Lynch, W. G. Sanger, S. Pirruccello, B. Quinn-Laquer, and D. D. Weisenburger Familial Multiple Myeloma: a Family Study and Review of the Literature J Natl Cancer Inst, October 3, 2001; 93(19): 1479 - 1483. [Abstract] [Full Text] [PDF]