{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T06:10:38Z","timestamp":1793340638285,"version":"4.5.0"},"reference-count":41,"publisher":"BMJ","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2012,12,24]]},"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                     <jats:italic>CDKN2A<\/jats:italic> and <jats:italic>CDK4<\/jats:italic> are high risk susceptibility genes for cutaneous malignant melanoma. Melanoma families with <jats:italic>CDKN2A<\/jats:italic> germline mutations have been extensively characterised, whereas <jats:italic>CDK4<\/jats:italic> families are rare and lack a systematic investigation of their phenotype.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>All known families with <jats:italic>CDK4<\/jats:italic> germline mutations (n=17) were recruited for the study by contacting the authors of published papers or by requests via the Melanoma Genetics Consortium (GenoMEL). Phenotypic data related to primary melanoma and pigmentation characteristics were collected. The <jats:italic>CDK4<\/jats:italic> exon 2 and the complete coding region of the <jats:italic>MC1R<\/jats:italic> gene were sequenced.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Eleven families carried the <jats:italic>CDK4<\/jats:italic> R24H mutation whereas six families had the R24C mutation. The total number of subjects with verified melanoma was 103, with a median age at first melanoma diagnosis of 39\u2005years. Forty-three (41.7%) subjects had developed multiple primary melanomas (MPM). A <jats:italic>CDK4<\/jats:italic> mutation was found in 89 (including 62 melanoma cases) of 209 tested subjects. <jats:italic>CDK4<\/jats:italic> positive family members (both melanoma cases and unaffected subjects) were more likely to have clinically atypical nevi than <jats:italic>CDK4<\/jats:italic> negative family members (p&lt;0.001). MPM subjects had a higher frequency of <jats:italic>MC1R<\/jats:italic> red hair colour variants compared with subjects with one tumour (p=0.010).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our study shows that families with <jats:italic>CDK4<\/jats:italic> germline mutations cannot be distinguished phenotypically from <jats:italic>CDKN2A<\/jats:italic> melanoma families, which are characterised by early onset of disease, increased occurrence of clinically atypical nevi, and development of MPM. In a clinical setting, the <jats:italic>CDK4<\/jats:italic> gene should therefore always be examined when a melanoma family tests negative for <jats:italic>CDKN2A<\/jats:italic> mutation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmedgenet-2012-101455","type":"journal-article","created":{"date-parts":[[2013,2,5]],"date-time":"2013-02-05T22:38:36Z","timestamp":1360103916000},"page":"264-270","source":"Crossref","is-referenced-by-count":131,"title":["Melanoma prone families with <i>CDK4<\/i> germline mutation: phenotypic profile and associations with <i>MC1R<\/i> variants"],"prefix":"10.1136","volume":"50","author":[{"given":"Hanne Eknes","family":"Puntervoll","sequence":"first","affiliation":[{"name":"Section for Pathology, The Gade Institute, University of Bergen, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong R","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hildegunn H\u00f8berg","family":"Vetti","sequence":"additional","affiliation":[{"name":"Western Norway Familial Cancer Center, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingeborg M","family":"Bachmann","sequence":"additional","affiliation":[{"name":"Section for Pathology, The Gade Institute, University of Bergen, Bergen, Norway"},{"name":"Department of Dermatology, Haukeland University Hospital, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Fran\u00e7oise","family":"Avril","sequence":"additional","affiliation":[{"name":"AP-HP, H\u00f4pital Cochin-Tarnier, Universit\u00e9 Paris Descartes, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meriem","family":"Benfodda","sequence":"additional","affiliation":[{"name":"AP-HP, Genetic Department, Bichat Hospital and INSERM U976, Cutaneous Research Center, Paris 7 University, Saint Louis Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Catrical\u00e0","sequence":"additional","affiliation":[{"name":"Department of Dermatologic Oncology, San Gallicano Dermatologic Institute, IRCCS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Dalle","sequence":"additional","affiliation":[{"name":"Unit of Dermatology, Universit\u00e9 Claude Bernard Lyon 1, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne B","family":"Duval-Modeste","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Rouen University Hospital, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Ghiorzo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genoa and Laboratory of Genetics of Rare Hereditary Cancers, San Martino-IST Research Hospital, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Grammatico","sequence":"additional","affiliation":[{"name":"Medical Genetics, Molecular Medicine Department, Sapienza University, S. Camillo-Forlanini Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Harland","sequence":"additional","affiliation":[{"name":"Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Leeds Cancer Research UK Centre, St James's University Hospital, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas K","family":"Hayward","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Han","family":"Hu","sequence":"additional","affiliation":[{"name":"AP-HP, Genetic Department, Bichat Hospital and INSERM U976, Cutaneous Research Center, Paris 7 University, Saint Louis Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Jouary","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Canc\u00e9rologie Cutan\u00e9e, Service de Dermatologie, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanguy","family":"Martin-Denavit","sequence":"additional","affiliation":[{"name":"Unit of Dermatology, Universit\u00e9 Claude Bernard Lyon 1, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aija","family":"Ozola","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane M","family":"Palmer","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenza","family":"Pastorino","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genoa and Laboratory of Genetics of Rare Hereditary Cancers, San Martino-IST Research Hospital, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dace","family":"Pjanova","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadem","family":"Soufir","sequence":"additional","affiliation":[{"name":"AP-HP, Genetic Department, Bichat Hospital and INSERM U976, Cutaneous Research Center, Paris 7 University, Saint Louis Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solrun J","family":"Steine","sequence":"additional","affiliation":[{"name":"Section for Pathology, The Gade Institute, University of Bergen, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J","family":"Stratigos","sequence":"additional","affiliation":[{"name":"Dermato-Oncology Unit, Department of Dermatology, University of Athens Medical School, Andreas Sygros Hospital, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Thomas","sequence":"additional","affiliation":[{"name":"Unit of Dermatology, Universit\u00e9 Claude Bernard Lyon 1, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Tinat","sequence":"additional","affiliation":[{"name":"Department of Genetics, Rouen University Hospital, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hensin","family":"Tsao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Wellman Center for Photomedicine, MGH Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u016bta","family":"Veinalde","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A","family":"Tucker","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Bressac-de Paillerets","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, D\u00e9partement de Biopathologie, Institut de Canc\u00e9rologie Gustave Roussy, Villejuif and INSERM U946, B\u00e2timent IGM, Fondation Jean Dausset, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia A","family":"Newton-Bishop","sequence":"additional","affiliation":[{"name":"Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Leeds Cancer Research UK Centre, St James's University Hospital, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa M","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars A","family":"Akslen","sequence":"additional","affiliation":[{"name":"Section for Pathology, The Gade Institute, University of Bergen, Bergen, Norway"},{"name":"Centre for Cancer Biomarkers, The Gade Institute, University of Bergen, Bergen, Norway"},{"name":"Department of Pathology, Haukeland University Hospital, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Molven","sequence":"additional","affiliation":[{"name":"Section for Pathology, The Gade Institute, University of Bergen, Bergen, Norway"},{"name":"Department of Pathology, Haukeland University Hospital, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2013,2,5]]},"reference":[{"key":"2025101711235686000_50.4.264.1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.11.999"},{"key":"2025101711235686000_50.4.264.2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0994-15"},{"key":"2025101711235686000_50.4.264.3","doi-asserted-by":"publisher","DOI":"10.1038\/nm0102-23"},{"key":"2025101711235686000_50.4.264.4","doi-asserted-by":"publisher","DOI":"10.1038\/ng0196-97"},{"key":"2025101711235686000_50.4.264.5","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20202"},{"key":"2025101711235686000_50.4.264.6","doi-asserted-by":"publisher","DOI":"10.1038\/366704a0"},{"key":"2025101711235686000_50.4.264.7","doi-asserted-by":"publisher","DOI":"10.1126\/science.7809631"},{"key":"2025101711235686000_50.4.264.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81400-2"},{"key":"2025101711235686000_50.4.264.9","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-0494"},{"key":"2025101711235686000_50.4.264.10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199510123331504"},{"key":"2025101711235686000_50.4.264.11","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.043802"},{"key":"2025101711235686000_50.4.264.12","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.2.209"},{"key":"2025101711235686000_50.4.264.13","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0b013e328014a2cd"},{"key":"2025101711235686000_50.4.264.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2006.11.016"},{"key":"2025101711235686000_50.4.264.15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2008.00446.x"},{"key":"2025101711235686000_50.4.264.16","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0b013e3283287d3e"},{"key":"2025101711235686000_50.4.264.17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2011.10551.x"},{"key":"2025101711235686000_50.4.264.18","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2012.01549.x"},{"key":"2025101711235686000_50.4.264.19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.30.18869"},{"key":"2025101711235686000_50.4.264.20","first-page":"5475","article-title":"The p16-cyclin D\/Cdk4-pRb pathway as a functional unit frequently altered in melanoma pathogenesis","volume":"56","author":"Bartkova","year":"1996","journal-title":"Cancer Res"},{"key":"2025101711235686000_50.4.264.21","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1034\/j.1600-0749.2000.130303.x","article-title":"The melanocortin 1 receptor (MC1R): more than just red hair","volume":"13","author":"Rees","year":"2000","journal-title":"Pigment Cell Res"},{"key":"2025101711235686000_50.4.264.22","doi-asserted-by":"publisher","DOI":"10.1038\/nature11624"},{"key":"2025101711235686000_50.4.264.23","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1111\/j.1600-0749.2005.00278.x","article-title":"Melanocortin-1 receptor structure and functional regulation","volume":"18","author":"Garcia-Borron","year":"2005","journal-title":"Pigment Cell Res"},{"key":"2025101711235686000_50.4.264.24","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20476"},{"key":"2025101711235686000_50.4.264.25","doi-asserted-by":"publisher","DOI":"10.1038\/ng1195-328"},{"key":"2025101711235686000_50.4.264.26","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.16.1701"},{"key":"2025101711235686000_50.4.264.27","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.10.1663"},{"key":"2025101711235686000_50.4.264.28","doi-asserted-by":"publisher","DOI":"10.1086\/302711"},{"key":"2025101711235686000_50.4.264.29","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-202x.2001.01421.x"},{"key":"2025101711235686000_50.4.264.30","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23396"},{"key":"2025101711235686000_50.4.264.31","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1158\/1055-9965.EPI-05-0321A","article-title":"Association of MC1R variants and risk of melanoma in melanoma-prone families with CDKN2A mutations","volume":"14","author":"Goldstein","year":"2005","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2025101711235686000_50.4.264.32","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-04-0777"},{"key":"2025101711235686000_50.4.264.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2010.01.027"},{"key":"2025101711235686000_50.4.264.34","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djq363"},{"key":"2025101711235686000_50.4.264.35","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22712"},{"key":"2025101711235686000_50.4.264.36","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1988.01670060015008"},{"key":"2025101711235686000_50.4.264.37","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03540420035026"},{"key":"2025101711235686000_50.4.264.38","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2008.00512.x"},{"key":"2025101711235686000_50.4.264.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2010.06.044"},{"key":"2025101711235686000_50.4.264.40","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2000.00823.x"},{"key":"2025101711235686000_50.4.264.41","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.72"}],"updated-by":[{"DOI":"10.1136\/jmedgenet-2012-101455corr1","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2014,2,14]],"date-time":"2014-02-14T00:00:00Z","timestamp":1392336000000}}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmedgenet-2012-101455","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T18:24:06Z","timestamp":1760725446000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmedgenet-2012-101455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,5]]},"references-count":41,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2013,3,13]]},"published-print":{"date-parts":[[2013,4]]}},"alternative-id":["10.1136\/jmedgenet-2012-101455"],"URL":"https:\/\/doi.org\/10.1136\/jmedgenet-2012-101455","relation":{"correction":[{"id-type":"doi","id":"10.1136\/jmedgenet-2012-101455corr1","asserted-by":"object"}]},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,5]]}}}