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KRAS mutations in brown tumor of the jaws in hyperparathyroidism
Author(s) -
Guimarães Letícia Martins,
Gomes Isadora Pereira,
Pereira Thaís dos Santos Fontes,
Andrade Bruno Augusto Benevenuto,
Romañach Mário José,
Lacerda Júlio César Tanos,
Pontes Hélder Antônio Rebelo,
Brennan Peter A.,
Rahimi Siavash,
Carlos Román,
MosquedaTaylor Adalberto,
BolognaMolina Ronell,
PassadorSantos Fabricio,
Gomez Ricardo Santiago,
Gomes Carolina Cavaliéri
Publication year - 2020
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.13048
Subject(s) - kras , cancer research , hyperparathyroidism , biology , pathogenesis , pathology , giant cell tumors , primary hyperparathyroidism , immunostaining , mapk/erk pathway , giant cell tumor of bone , giant cell , medicine , mutation , immunohistochemistry , signal transduction , endocrinology , genetics , gene
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 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.