Assessment of BRAFV600E and SMOF412E mutations in epithelial odontogenic tumours
Assessment of BRAFV600E and SMOF412E mutations in epithelial odontogenic tumours
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DOI：
10.1007/s13277-015-3238-0
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发表时间：
2015-07-01
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影响因子：
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通讯作者：
Gomez, Ricardo Santiago
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作者：
Diniz, Marina Goncalves;Gomes, Carolina Cavalieri;Gomez, Ricardo Santiago
多囊型或单囊型成釉细胞瘤的分类与其临床表现有关。最近，BRAF和SMO突变在成釉细胞瘤中被报道。然而，尚不清楚这些突变是否在成釉细胞瘤的多囊性和单囊性变异或牙源性癌中共享。我们评估了BRAFV600E和SMOF412E在多囊性、单囊性和结缔组织增生成釉细胞瘤中的作用。此外，我们还研究了BRAFV600E突变是否发生在牙源性癌中。共纳入28例福尔马林固定石蜡包埋标本，其中17例为成釉细胞瘤，11例为牙源性癌。BRAFV600E突变用TaqMan探针实时荧光定量PCR检测，Sanger测序证实。Sanger测序评估SMOF412E突变。17例成釉细胞瘤中有14例（82%）表现出BRAFV600E突变，具体而言，5/6（83%）为单囊性，7/9（78%）为多囊性，2/2为粘连性成釉细胞瘤。BRAFV600E突变在4/11（36%）恶性肿瘤中检测到，其中3/8（38%）成釉细胞癌和1/1透明细胞牙源性癌检测到BRAFV600E突变，而两种鬼细胞牙源性癌未检测到该突变。在成釉细胞瘤中未检测到SMOF412E突变。brafv600e激活突变在成釉细胞瘤中是一种常见的事件，无论发生在哪个部位或组织学类型。这种突变也在牙源性癌中发现。SMO体细胞突变是成釉细胞瘤发病过程中的继发性遗传事件。我们的研究结果支持了针对含有BRAFV600E突变的成釉细胞瘤和牙源性癌进行个体化、分子靶向治疗的可能性。
The classification of ameloblastoma in multicystic or unicystic variants is associated with its clinical behaviour. Recently, BRAF and SMO mutations have been reported in ameloblastomas. However, it is not clear if such mutations are shared by the multi-and unicystic variants of ameloblastoma or by odontogenic carcinomas. We assessed BRAFV600E and SMOF412E in multicystic, unicystic and desmoplastic ameloblastomas. In addition, we investigated whether the BRAFV600E mutation occurs in odontogenic carcinomas. A total of 28 formalin-fixed paraffin-embedded samples, comprising 17 ameloblastomas and 11 odontogenic carcinomas, were included. The BRAFV600E mutation was assessed by real-time PCR with a specific TaqMan probe and confirmed by Sanger sequencing. The SMOF412E mutation was assessed by Sanger sequencing. Fourteen out of 17 (82 %) ameloblastomas showed the BRAFV600E mutation, specifically, 5/6 (83 %) unicystic, 7/9 (78 %) multicystic and 2/2 desmoplastic ameloblastomas. BRAFV600E mutation was detected in 4/11 (36 %) malignant tumours, specifically, 3/8 (38 %) ameloblastic carcinomas and 1/1 clear cell odontogenic carcinoma, while the two ghost cell odontogenic carcinomas did not harbour this mutation. The SMOF412E mutation was not detected in ameloblastoma. The BRAFV600E-activating mutation is a common event in ameloblastomas, occurring regardless of site or histological type. This mutation is also detected in odontogenic carcinomas. SMO somatic mutation is a secondary genetic event in the ameloblastoma pathogenesis. Our findings support the possibility for personalised, molecular-targeted therapy for ameloblastomas and odontogenic carcinomas harbouring the BRAFV600E mutation.