Activating <i>FGFR2–RAS–BRAF</i> Mutations in Ameloblastoma

Brown, Noah A.; Rolland, Delphine C.M.; McHugh, Jonathan B.; Weigelin, Helmut C.; Zhao, Lili; Lim, Megan S.; Elenitoba-Johnson, Kojo S.J.; Betz, Bryan L.

doi:10.1158/1078-0432.ccr-14-1069

Cited by 225 publications

(410 citation statements)

References 43 publications

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“…Several studies have demonstrated activation of components of the MAPK pathway in an ameloblastoma cell line (AM-1) under various circumstances, including stimulation with tumor necrosis factor α and fibroblast growth factors-7 (FGF-7) and 10. [7] The presence of activating BRAF mutations indicates the role of a hyperactive RAS-RAF-MAPK pathway in the pathogenesis of ameloblastomas. [8] ERBB receptors are a receptor tyrosine kinase subfamily that includes the epidermal growth factor receptor (EGFR), ERBB2, ERBB3, and ERBB4.…”

Section: Oncogenesmentioning

confidence: 99%

A molecular insight in the prevalence of odontogenic tumor

Bhattacharjee¹,

Girish²,

Murgod³

et al. 2016

JCRI

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Odontogenic tumors (OT) encompass a diverse collection of lesions that ranges from hamartomas to benign and malignant neoplastic lesions of erratic aggressiveness. The progress and development of OT are influenced by variation of many kinds of genes and molecules. Genetic instability is a hallmark of cancer. This review illustrate a concurrent sketch of the recent updating of the molecular and genetic alterations linked with the growth and development of OT, including oncogenes, tumor-suppressor genes, oncoviruses, growth factors cell cycle regulators, apoptosis-related factors, regulators of tooth development, hard tissue-related proteins, cell adhesion molecules, matrixdegrading proteinases, factors of angiogenesis, and osteolytic cytokines. The logical and enhanced understanding of the molecular mechanism may provide newer thoughts for their recognition and administrate an improved prognosis of OT.

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Section: Oncogenesmentioning

confidence: 99%

A molecular insight in the prevalence of odontogenic tumor

Bhattacharjee¹,

Girish²,

Murgod³

et al. 2016

JCRI

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“…Dentre os diversos marcadores imunohistoquímicos estudados em associação com os ameloblastomas, as moléculas envolvidas com vias de sinalização celular tem sido demonstradas como principais ativadoras da proliferação celular desorganizada nesses tumores (Kurppa et al, 2014;Brown et al, 2014;Heikinheimo et al, 2015). Trabalhos recentes demonstraram uma alta frequência da proteína mutada BRAF associadas aos ameloblastomas mandibulares (Kurppa et al, 2014;Brown et al, 2014;Heikinheimo et al, 2015).…”

Section: Lista De Figurasunclassified

“…Trabalhos recentes demonstraram uma alta frequência da proteína mutada BRAF associadas aos ameloblastomas mandibulares (Kurppa et al, 2014;Brown et al, 2014;Heikinheimo et al, 2015). Essa mutação é denominada de BRAF V600E e ocorre devido a substituição do aminoácido valina para acido glutâmico no número 600 (Kurppa et al, 2014 Portanto, a detecção da mutação BRAF V600E abriu novas perspectivas na compreensão da etiopatogenia dos ameloblastomas bem como nas modalidades de tratamento com terapias alvo e abordagens menos agressivas.…”

Section: Lista De Figurasunclassified

“…Devido a esses fatores, estudos de marcadores moleculares associados aos ameloblastomas tem sido realizados com o intuito de desenvolver terapias sistêmicas visando a busca de tratamentos mais conservadores, sem a necessidade de cirurgias extensas e/ou repetitivas (Brown et al, 2014;Kurppa et al, 2014;Sweeney et al, 2014;Heikinheimo et al, 2015).…”

Section: Revisão De Literaturaunclassified

“…Já em ameloblastomas, o fator de crescimento epidérmico e o receptor de fator crescimento fibroblástico 2 se encontram especialmente aumentados (Brown et al, 2014;Kurppa et al 2014;Sweeney et al, 2014). A ativação desses receptores com os seus ligantes ocorrem no meio extracelular e uma vez ativados fora da célula, esses receptores contribuem para ativação das vias intracelulares.…”

Section: Revisão De Literaturaunclassified

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Análise imunohistoquímica da mutação BRAF V600E em ameloblastomas mandibulares

Canto¹

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Canto AM. Imunonhistochemical analysis of BRAF V600E mutation in ameloblastomas [Dissertation]. São Paulo: Universidade de São Paulo, Faculdade de Odontologia; 2017. Versão Original.Ameloblastoma is an aggressive odontogenic tumour, being locally invasive and highly recurrent. Studies have demonstrated that it is the most common benign odontogenic neoplasia, sometimes exhibiting behaviour of malignant lesions.Detection of BRAF V600E mutation has been shown to be one of the main proliferation pathways of ameloblastomas. Therefore, the identification of these markers can be useful to elaborate more efficient treatment strategies for this pathology as well as to improve the patient's quality of life. This study investigated the BRAF V600E mutation in mandible ameloblastomas by using the were male (52.38%) and 40 female (47.62%). The median age was 25.5 years old, with 42 cases having age below the median (50%) and 42 above it (50%). With regard to the presence or absence of BRAF V600E mutation, 66 cases were found to be positive for the marker (78.57%) and 18 were negative (21.43%). The correlation between BRAF expression and variables showed statistical significances for mandibular location (P = 0.0353) and tumour size (P = 0.008), whereas no statistical significance was observed for gender (P = 0.969), age (P = 1.0), radiographic aspect (P = 0.977), histological pattern (P = 0.910), histological subtype (P = 0.5141) and tumour status (P = 0.336). The authors concluded that BRAF V600E mutation is common in mandibular ameloblastomas, with tumours larger than four cm being more frequent in the posterior region of the mandible. In addition, this pathology occurs regardless of histological type of the tumour, age, gender, radiographic aspect and tumour status.

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Precision medicine: Sustained response to erdafitinib in FGFR2‐mutant, multiply recurrent ameloblastoma

Lawson-Michod

Tranesh

et al. 2022

Cancer Reports

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Background Ameloblastoma imposes significant morbidity and high‐recurrence rates following surgery and radiation therapy. Although 89% of cases harbor oncogenic mutations, the role of targeted therapy is undefined. Case We describe a case of a 40‐year‐old male with multiply recurrent, locally invasive ameloblastoma of the posterior maxillary ridge. The tumor was unresectable for negative margins due to extensive intracranial disease, and the patient suffered severe symptoms including pain. Immune and genomic profiling were obtained to guide systemic treatment, showing a PD‐L1 score of 2% and FGFR2 V395D and SMO W535L mutations. The patient progressed rapidly on anti‐PD1 immunotherapy. He was treated with the FGFR inhibitor, erdafitinib, with excellent partial response including resolution of intracranial disease and cancer‐related pain, ongoing 2 years after drug initiation. Conclusion Targeting the FGFR2 mutation resulted in sustained response and improved quality of life. Genomic profiling with targeted therapy for ameloblastoma appears promising, especially when surgery is technically infeasible.

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Activating FGFR2–RAS–BRAF Mutations in Ameloblastoma

Cited by 225 publications

References 43 publications

A molecular insight in the prevalence of odontogenic tumor

A molecular insight in the prevalence of odontogenic tumor

Análise imunohistoquímica da mutação BRAF V600E em ameloblastomas mandibulares

Precision medicine: Sustained response to erdafitinib in FGFR2‐mutant, multiply recurrent ameloblastoma

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