GSE120597
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 post-zygotic acquisition of NRAS alteration. However, large/giant CMN may exhibit phenotypic differences among distinct areas patients and in addition, patients differ in features such as presence of multiple CMN or Spilus-like lesions. Overall, 50 fresh-frozen biopsies corresponding to 37 phenotypically characterized areas of large/giant CMNs, 9 satellite lesions, 1 acquired nevus and 3 healthy skin biopsies were analyzed by a multigene panel and RNA sequencing (RNA-seq). Mutational screening showed mutations in 76.2% of large/giant CMN. NRAS mutation was found in 57.1% of cases, and mutations in other genes such as BRAF, KRAS, APC and MET were detected in 14.3% of patients. RNA-seq revealed the fusion transcript ZEB2-ALK and SOX5-RAF1 in large/giant CMN from two patients without point mutations. Both alterations were not detected in unaffected skin and were detected in different affected skin. These findings suggest that large/giant CMN may result from distinct molecular events in addition to NRAS mutations including point mutations and fusions transcripts. Overall design: Molecular characterization of 50 fresh-frozen biopsies by RNA-seq method. The set of biopsies includes 37 distinct areas from 19 large/giant CMNs patients,  9 satellite lesions, one acquired nevi and 3 healthy skin biopsies.