Melanoma with BRCA1::TMEM106A Fusion: A Novel Fusion Unprecedented in Melanoma

Summary: While Spitz melanocytic neoplasms frequently harbor chromosomal rearrangements resulting in recurrent gene fusions, non-Spitz melanomas typically lack such fusion events. Here, we report a unique case of a non-Spitz cutaneous melanoma harboring a BRCA1::TMEM106A fusion, a fusion transcript previously undescribed in melanoma. An 83-year-old man with multiple comorbidities, including Guillain-Barré syndrome and atrial fibrillation, presented with a pigmented nodule on his right posterior parietal scalp. A shave biopsy revealed ulcerated melanoma with a Breslow thickness of 3.4 mm, exhibiting both nodular and lentiginous growth patterns. The tumor cells demonstrated epithelioid and focally spindled morphologies. Next-generation sequencing (NGS) identified a BRCA1::TMEM106A fusion along with multiple somatic mutations, including TERT promoter mutation, and a tumor mutational burden of 88 mutations/Mb. Notably, although the melanoma lacked typical blue nevus-like melanoma (BNM) features, NGS also detected GNA11 S267F and GNAQ P127S mutations, suggesting the melanoma genetically aligns with BNM. A subsequent wide local excision showed scar with a focus of residual melanoma (pT3bNxM0), though sentinel lymph node biopsy was not performed due to the patient's comorbidities. To our knowledge, this represents the first report of a BRCA1::TMEM106A fusion in melanoma, contributing to the growing body of literature on fusion-associated melanomas of non-Spitz lineage.