Making sense of giant cell lesions of the jaws (GCLJ): lessons learned from next-generation sequencing |
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Authors: | Carolina C Gomes Marina G Diniz Victor C Bastos Vanessa F Bernardes Ricardo S Gomez |
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Affiliation: | 1. Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil;2. Department of Oral Surgery and Pathology, Faculty of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil |
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Abstract: | 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. |
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Keywords: | giant cell granuloma giant cell tumor of the bone non-ossifying fibroma cancer landscaping effects Noonan syndrome Jaffe–Campanacci syndrome bone tumor TRPV4 KRAS FGFR1 MAPK |
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