Abstract

BCR fusions as oncogenic drivers are primarily found in hematologic malignancies, such as chronic myeloid leukemia (CML). Since the discovery of BCR::ABL fusion in CML, several other BCR fusions with different fusion partners besides ABL have also been documented, including BCR::FGFR1, BCR::PDGFRA, BCR::RET, and BCR::JAK2. Little is known about BCR fusions in solid tumors. Herein, we report two cases of melanoma harboring novel BCR fusions, namely BCR::ZNF711 and BCR::CYLC2. The first case was from a 65-year-old male with melanoma on the right cheek/jaw (nodular type, ulcerated, Breslow thickness (BT): 4.2 mm). The tumor cells showed predominantly spindled cell morphology with fascicular growth pattern. Next-generation sequencing (NGS) revealed BCR::ZNF711 fusion with a high tumor mutational burden (TMB) of 31 mut/Mb. The second case was from a 74-year-old female with mucosal melanoma of the vagina (clinically 5 cm in greatest dimension; non-ulcerated, BT: at least 1.7 mm). The tumor cells exhibited predominantly epithelioid and focally nevoid morphologies. NGS revealed BCR::CYLC2 fusion with a TMB of 2 mut/Mb. Other fusions or mutations in BRAF, KIT, or NRAS were not identified in both cases. BCR fusions have been previously reported in a small subset of solid malignancies, albeit exceedingly rare, such as invasive mammary ductal carcinomas (BCR::MOV10L1, BCR::MRVI1) and oropharyngeal squamous cell carcinomas (BCR::TOM1, BCR::UPB1). To the best of our knowledge, our cases represent the first BCR fusions to be reported in melanomas, expanding the molecular spectrum of genetic alterations in melanomas.