sig_id path_name coalesce path_curator SIGNOR-MM Malignant Melanoma Melanoma is a skin cancer. It might exist as distinct subtypes associated with the activation of the MAPK and the PI3K pathways even if there is an association between distinct melanoma subtypes and molecular somatic events. Mucosal, acral, and to a lesser extent, lentigo malignant melanomas, can have increased copies of CDK4, and CCND1 (cyclinD), as well as mutations in KIT receptor. NRAS is mutated in about 18% of melanomas, and seems to be more frequently activated in nodular melanomas and melanomas due to chronic sun damage. BRAF has a recurrent V600E mutation (Gain of function) in about 50–70% of melanomas, however, this mutational event is frequently reported in benign pigmented naevi, and is not fully sufficient to induce a malignant transformation. MEK1 and MEK2 are downstream from RAS and RAF, on the same MAPK pathway. Activating mutations of MEK1 and MEK2 are found in 8% of melanomas. The PI3K pathway is activated through a PTEN loss-of-function mutation (most often deletion) in 20–40% of melanomas. Activating mutations or amplifications of PI3K or of AKT1 can also be found in some melanomas. Livia Perfetto