{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:56:01Z","timestamp":1790837761587,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,5,4]],"date-time":"2005-05-04T00:00:00Z","timestamp":1115164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2005,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in two loci encoding cell\u2010cycle\u2010regulatory proteins have been shown to cause familial malignant melanoma. About 20% of melanoma\u2010prone families bear a mutation in the <jats:italic>CDKN2A<\/jats:italic> locus, which encodes two unrelated proteins, p16INK4A and p14ARF. Mutations in the other locus, <jats:italic>CDK4<\/jats:italic>, are much rarer and have been linked to the disease in only three families worldwide. In the 1960s, a large Norwegian pedigree with multiple atypical nevi and malignant melanomas was identified. Subsequently, six generations and more than 100 family members were traced and 20 cases of melanoma verified. In this article, we report that <jats:italic>CDK4<\/jats:italic> codon 24 is mutated from CGT to CAT (Arg24His) in this unusually large melanoma kindred. Intriguingly, one of the family members had ocular melanoma, but the <jats:italic>CDK4<\/jats:italic> mutation could not be detected in archival tissue samples from this subject. Thus, the case of ocular melanoma in this family was sporadic, suggesting an etiology different from that of the skin tumors. The <jats:italic>CDK4<\/jats:italic> mutation in the Norwegian family was identical to that in melanoma families in France, Australia, and England. Haplotype analysis using microsatellite markers flanking the <jats:italic>CDK4<\/jats:italic> gene and single\u2010nucleotide polymorphisms within the gene did not support the possibility that there was a common founder, but rather indicated at least two independent mutational events. All <jats:italic>CDK4<\/jats:italic> melanoma families known to date have a substitution of amino acid 24. In addition to resulting from selection pressure, this observation may be explained by the CG dinucleotide of codon 24 representing a mutational hot spot in the <jats:italic>CDK4<\/jats:italic> gene. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20202","type":"journal-article","created":{"date-parts":[[2005,5,6]],"date-time":"2005-05-06T22:20:42Z","timestamp":1115418042000},"page":"10-18","source":"Crossref","is-referenced-by-count":94,"title":["A large Norwegian family with inherited malignant melanoma, multiple atypical nevi, and <i>CDK4<\/i> mutation"],"prefix":"10.1002","volume":"44","author":[{"given":"Anders","family":"Molven","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magne B.","family":"Grimstvedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solrun J.","family":"Steine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Harland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Fran\u00e7oise","family":"Avril","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas K.","family":"Hayward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars A.","family":"Akslen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,5,4]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"518","DOI":"10.2340\/0001555571518524","article-title":"Common and dysplastic naevi as risk factors for cutaneous malignant melanoma in a Swedish population","volume":"71","author":"Augustsson A","year":"1991","journal-title":"Acta Derm Venereol"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/303001"},{"key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1001\/archderm.1978.01640170032006","article-title":"Origin of familial malignant melanomas from heritable melanocytic lesions. \u2018The B\u2010K mole syndrome.\u2019","volume":"114","author":"Clark WH","year":"1978","journal-title":"Arch Dermatol"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.30.18869"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.16.8541"},{"key":"e_1_2_6_7_1","first-page":"537","article-title":"Further evidence for a locus for cutaneous malignant melanoma\u2010dysplastic nevus (CMM\/DN) on chromosome 1p, and evidence for genetic heterogeneity","volume":"52","author":"Goldstein AM","year":"1993","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.12.1006"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.2001.1944"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008390-200202000-00008"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9247"},{"key":"e_1_2_6_12_1","first-page":"1900","article-title":"Familial incidence of malignant melanoma","volume":"89","author":"Grimstvedt M","year":"1969","journal-title":"Tidsskr Nor Laegeforen"},{"key":"e_1_2_6_13_1","first-page":"869","article-title":"Dysplastic nevus syndrome of familial type. 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