Genomic and transcriptomic characterization of protein kinase C fusion melanocytes neoplasms with distinct hypo pigmented histomorphology

Summary: • We further expand the morphologic spectrum of PRKC fusion melanocytic tumors with molecular characterization. • Our 5 PRKC fusion tumors show biphasic morphology (dense epithelioid cells and loose spindle cells) with minimal to none melanin pigment. • We report fusion partners of PRKCA and PRKCB. • We identify transcriptomic differences from GNA driven blue nevus enriching in MITF-related gene set and TP53-related gene set. • PRKC fusion tumors demonstrate significantly stronger p53 IHC stain compared to blue nevi. • We demonstrate differences between PRKC fusion tumors and blue nevi on both RNA level and protein level. • Our novel transcriptome-level findings provide insight into the nuanced molecular events and new evidence for classification.