FREQUENT COEXISTENCE OF GLI1 OVEREXPRESSION AND BRAF(V600E) MUTATION IN AMELOBLASTOMAS

Abstract

Objective Recent studies show SMO mutations play a role in the pathogenesis in ameloblastomas and may co-existence with FGFR2, RAS and occasionally BRAF mutations. In our previous study, no SMO mutations were identified in ameloblastomas in Taiwan. To understand whether sonic hedgehog (SHH) pathway through other mechanisms is present in ameloblastomas in Taiwan and how frequent sonic hedgehog (SHH) pathway coexistence with BRAF mutation, we aimed to examine the expression of Gli1, the key transcription factor in SHH pathway, in ameloblastomas. Methods Thirty formalin fixed paraffin embedded ameloblastoma tissue sections were used for macro-dissection of tumor component and DNA and RNA extraction. Sanger sequencing was performed to detect the BRAF(V600E) and SMO(L412F and W535L) mutations. Real-time RT-PCR was performed to investigate the expression of Gli1. Four radicular cysts and one calcifying odontogenic cyst were used as controls. The relationship between Gli1 expression in ameloblastomas and clinicopathological parameters were also evaluated. Results Among 30 ameloblastoma cases, twenty-six cases harbored BRAF(V600E) mutation and none had SMO mutations. Either BRAF(V600) nor SMO mutations were identified in controls. The expression of Gli1 was significantly higher in ameloblastomas than controls (p 50 year-old than Conclusion Frequent coexistence of Gli1 overexpression and BRAF(V600E) mutation in ameloblastomas was noted.This finding suggested that inhibition of both SHH pathway and BRAF-MAPK pathway might be required for future target therapy in ameloblastomas.