CDK4 positive family members (both melanoma cases and unaffected subjects) were more likely to have clinically atypical nevi than CDK4 negative family members (p<0.001).
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.
To analyze <i>BRAF</i><sup>V600E</sup>, p16 expression and melanocyte proliferation in dermal, compound and dysplastic nevi, cells of primary and metastatic melanoma in the Polish population.
Using data from GenoMEL, we investigated the relationships between CDKN2A mutation carriage and 2-mm, 5-mm, and atypical nevus counts among blood-related members of melanoma families.
Conditional logistic regression, conditioning on families, was used to estimate the association between DN and each single-nucleotide polymorphism (SNP) separately, adjusted for age, sex, CMM, and CDKN2A status.
Among patients with melanoma genetically tested, CDKN2AG101W mutation carriers were more frequently younger (P = 0.023), with clinically atypical nevi (P = 0.050), with cytological atypia (P = 0.033) at confocal.
In CDKN2A-positive individuals, family history of CM and presence of atypical nevi, rather than MC1R status, modified risk (20.75- and 2.83-fold, respectively).
Altogether, the factors modifying significantly the melanoma risk associated with CDKN2A mutations (stepwise procedure) were: MC1R and dysplastic nevi (increasing the risk) and GSTT1 (decreasing the risk).
Multivariate analysis, using a stepwise selection procedure, showed significant effects of two factors on melanoma risk in CDKN2A mutations carriers: RHC variants [odds ratio of hazard function (OR), 2.21; P = 0.03] and dysplastic nevi (OR, 2.93; P < 0.01).
In these 53 families, three risk factors in addition to CDKN2A mutations increased melanoma risk: dysplastic nevi (OR = 2.32, 95% CI = 2.08 to 2.58), total nevi (OR = 1.99, 95% CI = 1.61 to 2.20) and sunburn (OR = 5.16, 95% CI = 4.82 to 5.52).
Genomic DNA was extracted from 39 biopsy samples (including primary melanomas, metastatic melanomas, and dysplastic nevi) from 25 patients in six Swedish families with a hereditary predisposition to melanoma who carried germline CDKN2A mutations.
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.
Although CDKN2A mutations confer substantial risk for melanoma, clinicoepidemiological covariates including dysplastic nevi (DN), total nevi, and solar injury also enhance melanoma risk.
However, there clearly are melanoma-prone families that do not express the dysplastic nevus trait, and some of the families linked to CDKN2A also present with dysplastic nevi.
Therefore, these data suggest that deletion of p16 may play an important role in the development of dysplastic nevus as an early event and that the changes may represent an early event in the development of malignant melanoma.
An absence of linkage between chromosome 9p markers and the 358delGCDKN2A mutation and DN was detected, indicating genetic heterogeneity for DN and CMM in this family.
Dermoscopy-targeted sampling and genotyping of a melanoma in situ arising in a dysplastic nevus revealed a phenotype-genotype paradox that confounds the exclusive significance of BRAF and NRAS mutations in melanoma pathogenesis.
Extended BRAF testing for 9 mutations in 125 dysplastic nevi from 101 patients, derived from populations with differing potential UV radiation exposure rates (Lebanon and Saudi Arabia), was performed.