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Melanoma-prone families: new evidence of distinctive clinical and histological features of melanomas in CDKN2A mutation carriers.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Gironi, Laura Cristina  ORCID logo  https://orcid.org/0000-0002-7298-4446
Colombo, Enrico 
Pasini, Barbara 
Giorgione, Roberto 
Farinelli, Pamela 

Abstract

Germline mutations on the CDKN2A gene, the most important known genetic factors associated with cutaneous melanomas (CMs), predispose carriers to multiple primary CMs (MPMs) with higher frequency and younger onset compared to non-carriers. Most of the largest published studies concerning clinical and histological characteristics of CMs with CDKN2A mutation carriers did not specify if the described CMs are first or subsequent to the first, and they used sporadic CMs from non-genotyped patients as controls. We conducted a single-centre observational study to compare clinical and histological CM features of 32 unrelated carriers (MUT) of 5 germline CDKN2A mutations (one of which was never previously described) compared to 100 genotyped wild-type (WT) patients. We stratified the data based on time of diagnosis, anatomical site and histological subtype of CMs, demonstrating several significant unreported differences between the two groups. MUT developed a higher number of dysplastic nevi and MPMs. We proved for the first time that anatomical distribution of CMs in MUT was independent of gender, unlike WTs. MUTs developed in situ and superficial spreading melanomas (SSMs) more frequently, with significantly higher number of SSMs on the head/neck. In MUTs, Breslow thickness was significantly lower for all invasive CMs. When CMs were stratified on the basis of the time of occurrence, statistical significance was maintained only for SSMs subsequent to the first. In WTs, Clark level was significantly higher, and ulceration was more prevalent than in MUTs. Significant differences in ulceration were observed only in SSMs. In nodular CMs, we did not find differences in terms of Breslow thickness or ulceration between WTs and MUTs. In situ CMs developed 10 years earlier in MUTs with respect to WTs, whereas no significant differences were observed in invasive CMs. In contrast to those reported previously by other authors, we did not find a difference in skin phototype.

Description

Keywords

CDKN2A, Cutaneous melanoma, Familial melanoma, Melanoma-susceptibility genes, Risk factor for cutaneous melanoma, Adult, Age Distribution, Biomarkers, Tumor, Case-Control Studies, Cyclin-Dependent Kinase Inhibitor p16, DNA Mutational Analysis, Female, Genetic Predisposition to Disease, Germ-Line Mutation, Heredity, Heterozygote, Humans, Italy, Male, Melanoma, Middle Aged, Pedigree, Phenotype, Risk Factors, Sex Distribution, Skin Neoplasms, White People, Young Adult

Journal Title

Arch Dermatol Res

Conference Name

Journal ISSN

0340-3696
1432-069X

Volume Title

310

Publisher

Springer Science and Business Media LLC