In:
Journal of Oral Pathology & Medicine, Wiley, Vol. 49, No. 8 ( 2020-09), p. 796-802
Abstract:
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 in TRPV4 , FGFR1 , and KRAS in 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 ( FGFR1 and KRAS ), 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 KRAS pathogenic mutations were detected in seven cases (p.G12V n = 4, p.G12D n = 1, p.G13D n = 1, p.A146T n = 1). KRAS variants of unknown significance (VUS), p.A134T and p.E37K, were also detected. All samples showed wild‐type sequences for FGFR 1 and TRPV4 genes. The activation of the MAPK/ERK signaling pathway was demonstrated by pERK1/2 immunohistochemical positivity of the brown tumors´ mononuclear cells. Conclusion Mutations in KRAS and 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.
Type of Medium:
Online Resource
ISSN:
0904-2512
,
1600-0714
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2026385-5
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