Melanoma
Genetic Abnormalities in Large to Giant Congenital Nevi: Beyond NRAS Mutations
Large and giant congenital melanocytic nevi (CMN) are rare melanocytic lesions mostly caused by postzygotic NRAS alteration. Molecular characterization is usually focused on NRAS and BRAF genes in a unique biopsy sample of the CMN. However, large/giant CMN may exhibit phenotypic differences among distinct areas, and patients differ in features such as presence of multiple CMN or spilus-like lesions. Herein, we have characterized a series of 21 large/giant CMN including patients with spilus-type nevi (9/21 patients, 42.8%).AURKA Overexpression Is Driven by FOXM1 and MAPK/ERK Activation in Melanoma Cells Harboring BRAF or NRAS Mutations: Impact on Melanoma Prognosis and Therapy
The cell cycle-related genes AURKA and FOXM1 are overexpressed in melanoma. We show here that AURKA overexpression is associated with poor prognosis in three independent cohorts of melanoma patients and correlates with the presence of genomic amplification of AURKA locus and BRAFV600E mutation. AURKA overexpression may also be driven by increased promoter activation through elements such as ETS and FOXM1 found within the 5′ proximal promoter region. Activated MAPK/ERK signaling pathway mediates robust AURKA promoter activation, thereby knockdown of BRAFV600E and ERK inhibition results in reduced AURKA transcription and expression.
