Journal of Peking University(Health Sciences) >
BRAF gene mutations in ameloblastic fibromas
Received date: 2018-10-11
Online published: 2019-02-26
Supported by
Supported by the National Natural Science Foundation of China(30901680);and the Fund for Fostering Young Scholars of Peking University Health Science Center(BMU2018PY023)
Objective: To investigate the BRAF gene mutations in ameloblastic fibroma (AF), and to further analyze the relationship between the BRAF mutation and clinical characteristics so as to provide new reference to the study of AF’s molecular pathology. Methods: Sixteen cases diagnosed as AF at the Department of Oral Pathology, Peking University School of Stomatology between January 1990 and December 2017 were collected. Genomic DNA was extracted from formalin-fixed, paraffin embedded tissues using the QIAamp DNA Mini Kit (Qiagen, Germany) according to the manufacturer’s instructions. Polymerase chain reaction (PCR) and direct sequencings were used to detect the BRAF gene mutations. The clinicopathological data, such as the age, location of the lesion, symptoms and treatments were retrospectively analyzed. Results: The sixteen cases of AF involved nine women and seven men aged 2-67 years. Three lesions occurred in the maxilla and thirteen in the mandible. The most common presenting symptom of AF was a painless slowly enlarging mass with swelling. Ten patients received conservative treatment and the other six patients received radical surgery. Three cases relapsed during the study period. BRAF gene mutation was found in sixteen of all the sixteen samples analyzed (100%). The BRAF mutation was a point mutation with a thymine-adenine transversion at nucleotide 1 799 of 15 exons, resulting in a change at residue 600 that substituted glutamine for valine. This mutation was the strongest activator of the downstream RAS/RAF/MEK/ERK-MAPK signaling pathway. This helped to bring about a gain-of-function mutation due to a V600E substitution. Many studies identified that BRAF regulated survival, apoptosis, and proliferation of cells by inducing MAPK pathways activation. For the existing cases, none of the age, sex, location, recurrence and treatments had a statistically significant correlation with BRAF mutation. Conclusion: Our findings demonstrated high prevalence of BRAF V600E mutation in AF. The pathogenic role remains to be clarified.
Key words： Ameloblastic fibroma; BRAF gene mutation; Targeted therapy
Zhu YOU , Li-li XU , Xue-fen LI , Jian-yun ZHANG , Jing DU , Li-sha SUN . BRAF gene mutations in ameloblastic fibromas[J]. Journal of Peking University(Health Sciences), 2019 , 51(1) : 4 -5 . DOI: 10.19723/j.issn.1671-167X.2019.01.002
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