Abstract

Giant congenital melanocytic nevi (CMN) are rare melanocytic lesions that are primarily caused by somatic mutations in NRAS or BRAF. Our cases characterize two giant CMN, one of which was a spilus-type nevi, that resulted in de novo melanomas. For each patient, we attained DNA sequencing and RNA fusion analysis for unaffected skin (CMN) and affected skin (melanoma) with germline testing. RNA sequencing revealed fusion transcript ZNF777-BRAF in the large congenital nevus and melanoma, with additional MET and TERT mutations in the melanoma. While the risk of melanoma varies between 1 – 15% for giant congenital nevi, this patient continually creates de novo melanomas suggesting that a fusion of BRAF with Zinc Finger Protein 777 greatly increases the risk of development of melanoma within a congenital melanocytic nevus.