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Making sense of giant cell lesions of the jaws (GCLJ): lessons learned from next‐generation sequencing
Author(s) -
Gomes Carolina C,
Diniz Marina G,
Bastos Victor C,
Bernardes Vanessa F,
Gomez Ricardo S
Publication year - 2020
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.5365
Subject(s) - kras , giant cell , biology , mutation , pathogenesis , somatic cell , genetics , pathology , medicine , immunology , gene
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.