Fusion of ALK to the melanophilin gene MLPH in pediatric Spitz nevi.

Fusion of ALK to the melanophilin gene MLPH in pediatric Spitz nevi.

Publication date: Mar 08, 2019

Spitzoid neoplasms typically affect young individuals and include Spitz nevus, atypical Spitz tumor and Spitzoid melanoma. Spitz tumors can exhibit gene fusions involving the receptor tyrosine kinases NTRK1, NTRK3, ALK, ROS1, RET, or MET, or, the serine-threonine kinase BRAF. Since most studies have been based on adult cases, we studied ALK fusions in Spitz nevi occurring in pediatric patients. 27 cases were screened for ALK expression by immunohistochemistry and 6 positive cases were identified. These cases were studied further using the TruSight RNA Fusion Panel and in 4 cases, exon 20 of the ALK gene was found to be fused to exon 14 of the MLPH (melanophilin) gene, a gene fusion that has only been reported in a Spitz nevus in an adult. The remaining 2 cases showed no fusion of ALK with any gene. The cases with the MLPH-ALK fusion showed a similar histology to that described for Spitz nevi with ALK fusions, with spindle-shaped and epithelioid melanocytes in fusiform nests with a plexiform growth pattern and infiltrative border. We created a breakapart FISH assay for MLPH and all 4 cases with the MLPH-ALK fusion were positive, while the other 23 cases in the study were negative. Thus, ALK and MLPH were fused only to each other in our series. Melanophilin is part of the melanosome trafficking apparatus together with MYO5a, TPM3 and RAB27a, all constitutively expressed in melanocytes. Kinase fusions involving MYO5a and TPM3 have been reported in Spitz tumors, and our series adds MLPH to this group.

Chung, C.T., Marrano, P., Swanson, D., Dickson, B.C., and Thorner, P.S. Fusion of ALK to the melanophilin gene MLPH in pediatric Spitz nevi. 21947. 2019 Hum Pathol.

Concepts Keywords
ALK ALK
Assay Spitz nevus
BRAF Melanophilin
Epithelioid ROS1
Exon Anaplastic lymphoma kinase
FISH Organ systems
Gene Branches of biology
Histology Tyrosine kinase receptors
Immunohistochemistry Spitz nevus
Kinase
Melanocytes
Melanoma
Melanosome
Neoplasms
Nevi
NTRK1
NTRK3
Pediatric
RET
Serine
Spindle
Spitz
Threonine
Tumor
Tyrosine

Semantics

Type Source Name
gene UNIPROT RAB27A
gene UNIPROT TPM3
gene UNIPROT MYO5A
gene UNIPROT SH3PXD2A
gene UNIPROT BRAF
drug DRUGBANK L-Threonine
drug DRUGBANK Serine
gene UNIPROT RNMT
gene UNIPROT MET
gene UNIPROT SLTM
drug DRUGBANK Methionine
gene UNIPROT RET
gene UNIPROT ROS1
gene UNIPROT NTRK3
gene UNIPROT NTRK1
drug DRUGBANK L-Tyrosine
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
disease MESH Spitz nevus
disease MESH neoplasms
disease MESH nevi
gene UNIPROT MLPH
gene UNIPROT ALK

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