A natural history of melanomas and dysplastic nevi

Abstract

BACKGROUND Few long‐term clinical and histologic data for melanocytic lesions have been available based on the mutation status of families at an increased risk of melanoma. In the current study, the authors describe the clinical and histologic features of dysplastic nevi and melanoma over time in families at an increased risk of melanoma with differing germline mutations in CDKN2A, CDK4, or not yet identified genes. METHODS Thirty‐three families with > 2 living members with invasive melanoma were evaluated clinically and followed prospectively for up to 25 years. All the participants were evaluated by the same study team at the Clinical Center of the National Institutes of Health or in local clinics. After informed consent was obtained, family members (n = 844) were examined and photographed. Blood was obtained for genetic studies; genotyping for CDKN2A and CDK4 was performed. Sequential photographs of melanocytic lesions were taken as part of the clinical evaluations. When melanocytic lesions were removed, the histology was reviewed. Representative photographs and photomicrographs were selected for six classes of lesions and three mutation groups. RESULTS All the families were found to have members with dysplastic nevi and melanoma; 17 had mutations in CDKN2A, 2 had mutations in CDK4, and 14 had no mutations in either gene identified. The majority of dysplastic nevi either remain stable or regress; few change in a manner that should cause concern for melanoma. With careful surveillance, melanomas can be found early. CONCLUSIONS The melanomas and dysplastic nevi that were found to occur in the study families did not appear to vary by the type of mutation identified in the families. Cancer 2002;94:3192–209. © 2002 American Cancer Society. DOI 10.1002/cncr.10605

Rare missense variants in POT1 predispose to familial cutaneous malignant melanoma

“…Detailed descriptions of these studies have been reported previously 27,31,32 . In brief, the Italian CMM family study evaluated in the exome sequencing and POT1 sequencing/genotyping analyses included 101 CMM cases/obligate carriers and 198 unaffected individuals from 56 CDKN2A/CDK4 -negative families with 2-5 affected relatives who were recruited at the Dermatology Unit of Maurizio Bufalini Hospital in Cesena, North-Eastern Italy.…”

Association of Genetic Variants in CDK6 and XRCC1 with the Risk of Dysplastic Nevi in Melanoma-Prone Families

“…Dysplastic nevi (DN) is a strong risk factor for melanoma and occur frequently in melanoma-prone families (Tucker et al , 2002). Previous studies have suggested a genetic component for DN, but to date no candidate genes have been identified.…”

“…However, there is a poor correlation within families between CDKN2A gene-carrier status and DN (Bishop et al , 2000; Cannon-Albright et al , 1994; Hussussian et al , 1994). In addition, DN occurs in melanoma-prone families with and without CDKN2A mutations with similar frequency (Tucker et al , 2002). These findings suggest that additional susceptibility genes or other genetic or epigenetic mechanisms involving CDKN2A contributing to the development of DN may exist in melanoma-prone families.…”

Management of familial occurrence of rare tumours: familial melanoma and multiple primary melanomas

“…Une é quipe nord-amé ricaine a surveillé 33 familles (844 personnes) pendant une pé riode allant jusqu'à 25 ans, 86 mé lanomes ont é té dé couverts chez 37 personnes dont 16 avaient dé jà eu un mé lanome (43 %). Soixante-dix-sept mé lanomes ont é té identifié s dans 19 familles avec mutation germinale connue (17 familles avec mutations de CDKN2A et deux familles avec mutations de CDK4) tandis que neuf mé lanomes é taient dé couverts dans 14 familles sans mutation identifié e [32]. Ces mé lanomes é taient de faible é paisseur (en moyenne 0,5 mm).…”