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Updated: Dec 28, 2025
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Clinical, pathological and dermoscopic phenotype of MITF p.E318K carrier cutaneous melanoma patients
Giulia Ciccarese1,2, Bruna Dalmasso1,2, William Bruno3,4
1IRCCS Ospedale Policlinico San Martino, Genetics of Rare Cancers, Genoa, Italy.
Background:
The p.E318K variant of the Melanocyte Inducing Transcription Factor (MITF) has been implicated in genetic predisposition to melanoma as an intermediate penetrance allele. However, the impact of this variant on clinico-phenotypic, as well as on dermoscopic patterns features of affected patients is not entirely defined. The purpose of our study was to assess the association between the p.E318K germline variant and clinic-phenotypical features of MITF+ compared to non-carriers (MITF-), including dermoscopic findings of melanomas and dysplastic nevi.
Methods:
we retrospectively analyzed a consecutive series of 1386 patients recruited between 2000 and 2017 who underwent genetic testing for CDKN2A, CDK4, MC1R and MITF germline variants in our laboratory for diagnostic/research purposes. The patients were probands of melanoma-prone families and apparently sporadic single or multiple primary melanoma patients. For all, we collected clinical, pathological information and dermoscopic images of the histopathologically diagnosed melanomas and dysplastic nevi, when available.
Results:
After excluding patients positive for CDKN2A/CDK4 pathogenic variants and those affected by non-cutaneous melanomas, our study cohort comprised 984 cutaneous melanoma patients, 22 MITF+ and 962 MITF-. MITF+ were more likely to develop dysplastic nevi and multiple primary melanomas. Nodular melanoma was more common in MITF+ patients (32% compared to 19% in MITF-). MITF+ patients showed more frequently dysplastic nevi and melanomas with uncommon dermoscopic patterns (unspecific), as opposed to MITF- patients, whose most prevalent pattern was the multicomponent.
Conclusions:
MITF+ patients tend to develop melanomas and dysplastic nevi with histopathological features, frequency and dermoscopic patterns often different from those prevalent in MITF- patients. Our results emphasize the importance of melanoma prevention programs for MITF+ patients, including dermatologic surveillance with digital follow-up.
Insights
The p.E318K variant in the Melanocyte Inducing Transcription Factor (MITF) gene is linked to melanoma predisposition. MITF+ carriers show distinct clinical and dermoscopic features in melanomas and dysplastic nevi, necessitating tailored prevention strategies.
Area of Science:
- Genetics and Genomics
- Dermatology
- Oncology
Background:
- The p.E318K variant of the Melanocyte Inducing Transcription Factor (MITF) is an intermediate penetrance allele associated with melanoma predisposition.
- The specific impact of this variant on clinical, phenotypic, and dermoscopic patterns in melanoma patients is not fully understood.
Purpose of the Study:
- To investigate the association between the p.E318K germline variant (MITF+) and clinic-phenotypic features.
- To compare dermoscopic patterns of melanomas and dysplastic nevi between MITF+ carriers and non-carriers (MITF-).
Main Methods:
- Retrospective analysis of 1386 patients with genetic testing for MITF and other melanoma-associated genes.
- Collection of clinical, pathological, and dermoscopic data for 984 cutaneous melanoma patients, categorized as MITF+ (22) and MITF- (962).
Main Results:
- MITF+ patients had a higher likelihood of developing dysplastic nevi and multiple primary melanomas.
- Nodular melanoma was more prevalent in MITF+ patients (32%) compared to MITF- patients (19%).
- Dysplastic nevi and melanomas in MITF+ patients frequently exhibited uncommon (unspecific) dermoscopic patterns, unlike the prevalent multicomponent pattern in MITF- patients.
Conclusions:
- MITF+ patients exhibit distinct histopathological and dermoscopic features in melanomas and dysplastic nevi.
- These findings underscore the need for enhanced melanoma prevention and surveillance programs, including digital follow-up, for MITF+ individuals.
