Title成釉细胞纤维瘤中BRAF突变基因的检测
Other TitlesBRAF gene mutations in ameloblastic fibromas
Authors尤柱
徐丽莉
李雪芬
张建运
杜菁
孙丽莎
Affiliation北京大学口腔医学院·口腔医院中心实验室国家口腔疾病临床医学研究中心口腔数字化医疗技术和材料国家工程实验室口腔数字医学北京市重点实验室
山东大学口腔医学院口腔颌面外科
北京大学口腔医学院·口腔医院第二门诊部
北京大学口腔医学院·口腔医院病理科
Keywords成釉细胞纤维瘤
BRAF基因突变
靶向治疗
Ameloblastic fibroma
BRAF gene mutation
Targeted therapy
Issue Date2019
Publisher北京大学学报(医学版)
Abstract目的:检测BRAF基因在成釉细胞纤维瘤(ameloblastic fibroma,AF)中的突变情况,进一步分析该突变与AF的临床表现之间的关系,以期为寻求AF的靶向治疗提供新方法。方法:收集2002年1月至2015年12月期间北京大学口腔医院诊断为AF的病例16例。AF石蜡包埋组织经切片后进行苏木精伊红染色,由两名病理科专家确认病例选取的准确性,按照DNA提取试剂盒使用说明提取组织DNA。对BRAF V600E位点进行PCR扩增,采用直接测序的方法进行BRAF V600E的突变检测,并进一步分析16例AF的临床资料。结果:16例AF患者中包括7例男性,9例女性; 3例发生于上颌,13例发生于下颌;入院年龄为2~67岁(中位年龄14. 5岁)。病变常表现为无痛性肿胀,生长缓慢。16例AF均携带BRAF基因突变,突变率为100%(16/16),均为15号外显子上V600E突变型(c. 1799T> A),导致在氨基酸水平上由缬氨酸变为谷氨酸,从而使胸腺嘧啶转化为腺苷酸。现有病例表明BRAF突变与AF的年龄、性别、发病部位和复发等无相关性。结论:AF中存在BRAF V600E位点的高突变率,提示BRAF V600E突变可能成为AF发生发展的关键事件,同时为AF患者应用BRAF抑制剂进行靶向治疗提供了一定的理论支持,其病理学意义有待进一步研究。
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 V600 E 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 V600 E mutation in AF. The pathogenic role remains to be clarified.
URIhttp://hdl.handle.net/20.500.11897/559986
ISSN1671-167X
DOI10.19723/j.issn.1671-167X.2019.01.002
Indexed中文核心期刊要目总览(PKU)
Appears in Collections:口腔医院

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