Clinical, dermoscopic, and confocal features of nevi and melanomas in a multiple primary melanoma patient with the MITF p.E318K homozygous mutation

The development of multiple primary melanomas (MPM) is suggestive of hereditary melanoma predisposition and has been associated with mutations in the high-penetrance susceptibility genes cyclin-dependent kinase inhibitor 2A (CDKN2A), cyclin-dependent kinase 4 (CDK4), and protection of telomeres 1 (POT1) and with variants in the intermediate-risk genes melanocortin-1 receptor (MC1R) and Microphthalmia-associated transcription factor (MITF) 1.

MITF is a transcription factor acting as a master gene of melanocyte homeostasis. The rare germline MITF p.E318K variant has been associated with melanoma and/or renal cell carcinoma 2-7. p.E318K interferes with MITF SUMOylation, resulting in enhanced MITF transcriptional activity, thus supporting an oncogenic role for MITF2, and reduces the program of senescence, potentially favoring melanoma progression in vivo8.

Sara Bassoli; Cristina Pellegrini; Caterina Longo, et al (Fargnoli)

Melanoma Research. 28(2):166-169, April 2018