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Author Spotlight: Integrating BRET-Based Assays and Rare Mutation Analysis to Decipher RAF Kinase Regulation in Live Cells
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Spitz tumor with RAF1 fusion: A report of 3 cases

Michele Donati1, Daniel Nosek2, Shantel Olivares3

  • 1Department of Pathology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.

Annals of Diagnostic Pathology
|October 19, 2023
PubMed

Insights

RAF1 fusions are identified in Spitz tumors, a type of melanocytic neoplasm. These findings suggest RAF1-fused melanocytic neoplasms may constitute a distinct subgroup of Spitz tumors, driven by RAF1 gene fusions.

Area of Science:

  • Dermatology
  • Oncology
  • Molecular Pathology

Background:

  • Spitz tumors are melanocytic neoplasms characterized by specific cellular and stromal changes.
  • Known genetic alterations include fusions of ALK, ROS1, NTRK, MET, RET, BRAF, MAP3K8, and HRAS mutations.
  • RAF1 fusions have recently been identified in various cutaneous melanocytic neoplasms.

Observation:

  • This study reports three cases of Spitz neoplasms harboring RAF1 fusions.
  • These include one previously described CTDSPL::RAF1 fusion and two novel fusions: PPAP2B::RAF1 and ATP2B4::RAF1.
  • Two cases were diagnosed as Spitz nevus, and one as Spitz melanoma.

Findings:

  • The identified RAF1 fusions (CTDSPL::RAF1, PPAP2B::RAF1, ATP2B4::RAF1) represent novel oncogenic drivers in melanocytic neoplasms.
  • The Spitz melanoma case exhibited 9p21 homozygous deletion and a positive sentinel lymph node biopsy.
  • RAF1-fused melanocytic neoplasms may represent a distinct clinicopathological entity.

Implications:

  • RAF1 fusions could define a new molecular subgroup within Spitz tumors.
  • Understanding these genetic drivers is crucial for accurate diagnosis and potential targeted therapies.
  • This research expands the spectrum of genetic alterations associated with Spitz neoplasms.
Keywords:
RAF1 fusionSpitz tumorUnusual melanocytic neoplasmsspitzoid morphology

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