期刊
JOURNAL OF ORAL PATHOLOGY & MEDICINE
卷 49, 期 8, 页码 796-802出版社
WILEY
DOI: 10.1111/jop.13048
关键词
bone tumor; giant cell lesions; hyperparathyroidism; MAPK; ERK pathway; mutations
资金
- Coordination for the Improvement of Higher Level Education Personnel (CAPES)/Brazil [001]
- National Council of Scientific and Technological Development (CNPq)/Brazil
- Research Support Foundation of the State of Minas Gerais (FAPEMIG)/Brazil
Background Brown tumors are giant cell-rich lesions that result from abnormal bone metabolism in hyperparathyroidism, one of the most common endocrine disorders worldwide. Brown tumors occasionally affect the jaws and, despite well-known clinical and microscopic features, their molecular pathogenesis remains unclear. We investigated the presence of pathogenic activating mutations inTRPV4,FGFR1, andKRASin a cohort of brown tumors since these have recently been reported in giant-cell lesions of the jaws and non-ossifying fibromas of the bones (FGFR1andKRAS), which are histologic mimics of brown tumors. Methods We target sequenced 13 brown tumors of the jaws associated with primary or secondary hyperparathyroidism. As mutations in these genes are known to activate the MAPK/ERK signaling pathway, we also assessed the immunostaining of the phosphorylated form of ERK1/2 (pERK1/2) in these lesions. Results KRASpathogenic mutations were detected in seven cases (p.G12V n = 4, p.G12D n = 1, p.G13D n = 1, p.A146T n = 1).KRASvariants of unknown significance (VUS), p.A134T and p.E37K, were also detected. All samples showed wild-type sequences forFGFR1 andTRPV4genes. The activation of the MAPK/ERK signaling pathway was demonstrated by pERK1/2 immunohistochemical positivity of the brown tumors ' mononuclear cells. Conclusion Mutations inKRASand activation of the MAPK/ERK signaling pathway were detected in brown tumors of hyperparathyroidism of the jaws, expanding the spectrum of giant cell lesions whose molecular pathogenesis involve RAS signaling.
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