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Journal of Peking University(Health Sciences) ›› 2019, Vol. 51 ›› Issue (1): 4-5. doi: 10.19723/j.issn.1671-167X.2019.01.002

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BRAF gene mutations in ameloblastic fibromas

Zhu YOU1,2,Li-li XU3,Xue-fen LI1,Jian-yun ZHANG4,Jing DU2,Li-sha SUN1,△()   

  1. 1. Department of Central Laboratory, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
    2. Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, Jinan 250012, China
    3. Second Clinical Division, Peking University School and Hospital of Stomatology, Beijing 100081, China
    4. Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing 100081, China
  • Received:2018-10-11 Online:2019-02-18 Published:2019-02-26
  • Contact: Li-sha SUN E-mail:lisa_sun@bjmu.edu.cn
  • 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)

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Abstract:

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

CLC Number: 

  • R739.8

Table 1

Clinical features of the 16 studied ameloblastic fibroma cases"

Case No. Age/ years Gender Site Symptoms Treatment Recurrence
1 23 F Left mandible Swelling Curettage Recurrent, 14 years
2 28 F Right mandible Swelling Lost to follow-up Lost to follow up
3 26 M Right mandible Chin swelling
and numbness		 Right mandibular segmental osteo-
tomy and right iliac crest bone graft		 Recurrent, 1 month
4 13 F Right mandible Swelling Right mandibular segmental osteotomy
and right fibula flap repair		 Lost to follow up
5 20 F Left mandible Swelling, firm Left mandibular segmental osteotomy
and left fibula flap repair		 Lost to follow up
6 1 M Right maxilla Swelling Curettage Non recurrent, 3 years
7 6 M Right maxilla Swelling Curettage Lost to follow up
8 13 F Right mandible Swelling, firm Curettage Non recurrent, 3 years
9 2 M Left mandible Swelling Curettage Non recurrent,1 year
10 3 F Right maxilla Swelling Curettage Non recurrent, 7 months
11 12 F Right mandible Cystic neoplasm Curettage Non recurrent, 4 months
12 22 F Left mandible Swelling, firm Curettage Recurrent, 40 months
13 67 M Right mandible Swelling, firm,
adhering to the bone		 Right mandibular segmental osteotomy
and left fibula flap repair		 Non recurrent, 3 years
14 41 M Left mandible Swelling, repeated
decline and growth		 Left mandibular segmental osteotomy
and left fibula flap repair		 Non recurrent,16 months
15 16 M Right mandible Cystic neoplasm Curettage Non recurrent, 21 months
16 6 F Left mandible Swelling Curettage Non recurrent, 6 years

Figure 1

Assessment of BRAF mutations in ameloblastic fibroma A, PCR amplification with AB 3730xl identifies a BRAF exon 15 mutation encoding p.Val600Glu; B, wide-type BRAF of the normal tissue."

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