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• W3136130198 endingPage "115935" @default.
• W3136130198 startingPage "115935" @default.
• W3136130198 abstract "The majority of giant cell lesions of the jaw present as a solitary focus of disease in bones of the maxillofacial skeleton. Less frequently they occur as multifocal lesions. This raises the clinical dilemma if these should be considered distinct entities and therefore each need a specific therapeutic approach. Solitary giant cell lesions of the jaw present with a great diversity of symptoms. Recent molecular analysis revealed that these are associated with somatic gain-of-function mutations in KRAS, FGFR1 or TRPV4 in a large component of the mononuclear stromal cells which all act on the RAS/MAPK pathway. For multifocal lesions, a small group of neoplastic multifocal giant cell lesions of the jaw remain after ruling out hyperparathyroidism. Strikingly, most of these patients are diagnosed with jaw lesions before the age of 20 years, thus before the completion of dental and jaw development. These multifocal lesions are often accompanied by a diagnosis or strong clinical suspicion of a syndrome. Many of the frequently reported syndromes belong to the so-called RASopathies, with germline or mosaic mutations leading to downstream upregulation of the RAS/MAPK pathway. The other frequently reported syndrome is cherubism, with gain-of-function mutations in the SH3BP2 gene leading through assumed and unknown signaling to an autoinflammatory bone disorder with hyperactive osteoclasts and defective osteoblastogenesis. Based on this extensive literature review, a RAS/MAPK pathway activation is hypothesized in all giant cell lesions of the jaw. The different interaction between and contribution of deregulated signaling in individual cell lineages and crosstalk with other pathways among the different germline- and non-germline-based alterations causing giant cell lesions of the jaw can be explanatory for the characteristic clinical features. As such, this might also aid in the understanding of the age-dependent symptomatology of syndrome associated giant cell lesions of the jaw; hopefully guiding ideal timing when installing treatment strategies in the future." @default.
• W3136130198 created "2021-03-29" @default.
• W3136130198 creator A5010615884 @default.
• W3136130198 creator A5020765459 @default.
• W3136130198 creator A5032909516 @default.
• W3136130198 creator A5069899921 @default.
• W3136130198 date "2021-08-01" @default.
• W3136130198 modified "2023-10-13" @default.
• W3136130198 title "Multiple versus solitary giant cell lesions of the jaw: Similar or distinct entities?" @default.
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