Making sense of giant cell lesions of the jaws (GCLJ): lessons learned from next-generation sequencing
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Universidade Federal de Minas Gerais
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Artigo de periódico
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Resumo
Next-generation sequencing has revealed mutations in several bone-related lesions and was recently used to uncover the genetic basis of giant cell lesions of the jaws (GCLJ). Consistent with their benign nature, GCLJ show a low tumor mutation burden. They also harbor somatic, heterozygous, mutually exclusive mutations in TRPV4, KRAS, or FGFR1. These signature mutations occur only in a subset of lesional cells, suggesting the existence of a 'landscaping effect', with mutant cells inducing abnormal accumulation of non-mutant cells that form the tumor mass. Osteoclast-rich lesions with histological similarities to GCLJ can occur in the jaws sporadically or in association with genetically inherited syndromes. Based on recent results, the pathogenesis of a subgroup of sporadic GCLJ seems closely related to non-ossifying fibroma of long bones, with both lesions sharing MAPK pathway-activating mutations. In this review, we extrapolate from these recent findings to contextualize GCLJ genetics and we highlight the therapeutic implications of this new information. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Abstract
Assunto
Receptor, Fibroblast Growth Factor, type 1, Genes, ras, Mitogen-Activated Protein Kinases, Noonan syndrome, Bone neoplasms, Granuloma, giant cell, Giant cell tumor of bone, Jaw, Mutation, Genetics, Therapeutics
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FGFR1, Jaffe-Campanacci syndrome, KRAS, MAPK, Noonan syndrome, TRPV4, Bone tumor, Cancer landscaping effects, Giant cell granuloma, Giant cell tumor of the bone, Non-ossifying fibroma
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https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.5365