{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T02:52:34Z","timestamp":1761101554115,"version":"3.37.3"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2001,8,28]],"date-time":"2001-08-28T00:00:00Z","timestamp":998956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002738","name":"AP-HP","doi-asserted-by":"crossref","award":["CRC96011"],"award-info":[{"award-number":["CRC96011"]}],"id":[{"id":"10.13039\/501100002738","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fondation Sanofi Vaincre le M\u00e9lanome"},{"name":"Association pour la Recherche contre le Cancer (ARC) Subvention libre 1998"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2001,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multiple primary cancers are one of the hallmarks of inherited predisposition. Outside the familial context, multiple primary tumors could be related either to germline de novo mutations or to low\u2010penetrance mutations, in predisposing genes. We selected 100 patients who displayed multiple primary melanoma (MPM) without any known melanoma cases recorded within their families and looked for germline mutations in the two melanoma\u2010predisposing genes identified to date, <jats:italic>CDKN2A<\/jats:italic> and <jats:italic>CDK4<\/jats:italic> exon 2. Nine patients (9%) had germline mutations in <jats:italic>CDKN2A<\/jats:italic>, whereas none carried germline mutations in exon 2 of <jats:italic>CDK4<\/jats:italic>. Seven cases displayed a recurrent missense mutation, G101W, already described in more than 20 melanoma\u2010prone families; one case carried a missense mutation never reported to date (P114S), and the last case was a carrier of a 6 bp insertion at nucleotide 57 resulting in a duplication of codons 18 and 19. To ascertain whether the G101W was a mutational hot spot for de novo mutations or a common founder mutation, we genotyped eight microsatellite markers flanking the <jats:italic>CDKN2A<\/jats:italic> gene. After allowing for recombination over time, haplotype sharing provided evidence for an original G101W mutation common to 6 out of 7 sporadic MPM cases. Therefore, it can be concluded that de novo germline <jats:italic>CDKN2A<\/jats:italic> mutations associated with MPM are rare. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.1183","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T21:15:54Z","timestamp":1030310154000},"page":"195-202","source":"Crossref","is-referenced-by-count":53,"title":["Sporadic multiple primary melanoma cases: <i>CDKN2A<\/i> germline mutations with a founder 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