The role of gene fusions in melanocytic neoplasms.

The role of gene fusions in melanocytic neoplasms.

Publication date: Jun 01, 2019

Recent advances in next generation sequencing (NGS) have allowed for efficient whole transcriptome sequencing, leading to the identification of important kinase fusions as the primary driver in some melanocytic neoplasms. These fusions typically occur mutually exclusively of one another and other well-known initiating mutations such as BRAF, NRAS, NF1, KIT, and GNAQ. Fusions are found in over 50% of Spitz neoplasms, including ALK, BRAF, NTRK1, NTRK3, ROS1, MET, MAP3K8, and RET. Familiarity with the typical morphologic features of certain fusion-driven melanocytic neoplasms can help with classification, diagnosis, and identification of targeted molecular therapies in malignant cases. Spitz tumors with ALK, NTRK1, and NTRK3 fusions have characteristic morphologic features. BRAF and MAP3K8 fusions, in particular, tend to be epithelioid, high grade, and more frequent in Spitz melanoma than other fusion subtypes. Sporadic cases of pigmented epithelioid melanocytoma may have PRKCA fusions and sheets of monomorphic epithelioid melanocytes. Fusion events are also enriched among melanomas without the key mutations BRAF, NRAS, or NF1. Although NGS is the most reliable method to detect fusions, immunohistochemistry and fluorescence in situ hybridization are cost-effective alternatives in some cases. We describe recent discoveries regarding the role of kinase fusions in melanocytic neoplasms and their associated morphologies. This article is protected by copyright. All rights reserved.

Quan, V.L., Panah, E., Zhang, B., Shi, K., Mohan, L.S., and Gerami, P. The role of gene fusions in melanocytic neoplasms. 22841. 2019 J Cutan Pathol.

Concepts Keywords
ALK Epithelioid
BRAF Spitz nevus
Epithelioid ROS1
Fluorescence Organ systems
Hybridization Branches of biology
Immunohistochemistry Tyrosine kinase receptors
Kinase Hybridization
KIT Melanoma
Malignant
Melanocytes
Melanoma
Melanomas
Monomorphic
Morphologic
Neoplasms
NF1
NTRK1
NTRK3
RET
Sequencing
Spitz
Transcriptome

Semantics

Type Source Name
gene UNIPROT PRKCA
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
disease MESH diagnosis
gene UNIPROT RET
gene UNIPROT MAP3K8
gene UNIPROT RNMT
gene UNIPROT MET
gene UNIPROT SLTM
drug DRUGBANK Methionine
gene UNIPROT ROS1
gene UNIPROT NTRK3
gene UNIPROT NTRK1
gene UNIPROT ALK
gene UNIPROT GNAQ
gene UNIPROT KIT
gene UNIPROT NF1
gene UNIPROT NRAS
gene UNIPROT BRAF
disease MESH neoplasms

Original Article

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