title: Pigment-Synthesizing Melanocytic Neoplasm With Protein Kinase C Alpha (PRKCA) Fusion.
abstract: OBJECTIVE
  Melanocytic neoplasms with prominent pigment synthesis mimicking equine melanoma represent a rare variant of biologically indeterminate or low-grade malignant melanocytic tumors in which the molecular profile and exact histologic classification are not established. Tumors with these characteristics rarely occur as congenital lesions. We performed genomic analysis of a congenital pigment synthesizing melanocytic neoplasm with indeterminate biological potential.
  
  
  METHODS
  The patient was a 5-month-old girl presenting with a 6-cm protuberant scalp mass, which had doubled in size since birth. Histologic examination showed heavily pigmented intradermal proliferation of large, epithelioid melanocytes with mild cytologic atypia, low mitotic activity, focal necrosis, and ulceration. RNA sequencing identified a novel ATPase, Ca2+ transporting, plasma membrane 4(ATP2B4)-protein kinase C-alpha (PRKCA) fusion transcript. The fusion resulted in an in-frame linkage of the PRKCA catalytic domain with the N-terminal of ATP2B4 and high expression of the PRKCA kinase domain. Break-apart fluorescence in situ hybridization showed PRKCA rearrangement, and reverse transcriptase-polymerase chain reaction confirmed the presence of the fusion transcript. The patient was alive and well, with no evidence of recurrence, at the 1-year follow-up.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report of PRKCA fusions in melanocytic neoplasms. Future studies need to determine the frequency of PRKCA fusions in pigment-synthesizing melanocytic neoplasms.
authors.affiliation: Department of Pathology, St Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Armita
authors.initials: A
authors.lastname: Bahrami
authors.affiliation: Department of Pathology, St Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Seungjae
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Computational Biology, St Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Pathology, Loma Linda University, Loma Linda, California.
authors.forename: Justin
authors.initials: J
authors.lastname: Kerstetter
authors.affiliation: Department of Pathology, Loma Linda University, Loma Linda, California.
authors.forename: Maral
authors.initials: M
authors.lastname: Rahvar
authors.affiliation: Department of Pathology, University of California-Los Angeles.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Computational Biology, St Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: John
authors.initials: J
authors.lastname: Easton
authors.affiliation: Department of Computational Biology, St Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Institute Curie, Paris, France.
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Barnhill
mesh_terms: D005260:Female; D006801:Humans; D007223:Infant; D008544:Melanocytes / Q000473:pathology; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D050576:Membrane Fusion Proteins / Q000235:genetics*; D009508:Nevus, Pigmented / Q000235:genetics* / Q000473:pathology; D051571:Protein Kinase C-alpha / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics*; D012535:Scalp; D017423:Sequence Analysis, RNA; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D050576:Membrane Fusion Proteins; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506943:ATP2A1 protein, human