Making sense of giant cell lesions of the jaws (GCLJ): lessons learned from next-generation sequencing.
J Pathol
; 250(2): 126-133, 2020 02.
Article
in En
| MEDLINE
| ID: mdl-31705763
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Jaw Neoplasms
/
Giant Cell Tumors
Limits:
Humans
Language:
En
Journal:
J Pathol
Year:
2020
Document type:
Article
Affiliation country:
Brasil