EVALUATION OF TERT PROMOTER HOTSPOT MUTATIONS IN AMELOBLASTOMA AND AMELOBLASTIC CARCINOMA

Abstract

Ameloblastoma is a benign, locally destructive, and infiltrative neoplasm. Ameloblastic carcinoma (AC) is a rare malignant tumor that arises either de novo or from a pre-existing ameloblastoma. The gene telomerase reverse transcriptase (TERT) encodes the enzyme telomerase, responsible for preventing replicative senescence. Detectable telomerase activity has been reported in ameloblastoma. TERT promoter (TERTp) mutation is one of the mechanisms that lead to increased enzyme activity. The coexistence of TERTp mutations with BRAFV600E is reported in some tumors as papillary thyroid carcinoma or cutaneous melanoma, and it is associated with aggressiveness. Ameloblastoma and AC harbor BRAFV600E, however, it remains unknown whether these odontogenic tumors also show mutations in TERT promoter. Objective: To investigate TERTp hotspot mutations in ameloblastoma and AC. Study Design: Genomic DNA of paraffin-embedded ameloblastomas (n=6) and AC (n=3) were Sanger-sequenced to assess the hotspot mutations C228T and C250T TERTp. Results: None of the samples harbored TERTp mutations. Conclusion: The results suggest that the mutations C228T and C250T in TERT promoter are not a common event in ameloblastoma and AC. Whether other genetic or epigenetic events in TERT promoter play a role in the tumorigenesis of these odontogenic tumors remains to be elucidated. SUPPORT: FAPEMIG PROBIC. Ameloblastoma is a benign, locally destructive, and infiltrative neoplasm. Ameloblastic carcinoma (AC) is a rare malignant tumor that arises either de novo or from a pre-existing ameloblastoma. The gene telomerase reverse transcriptase (TERT) encodes the enzyme telomerase, responsible for preventing replicative senescence. Detectable telomerase activity has been reported in ameloblastoma. TERT promoter (TERTp) mutation is one of the mechanisms that lead to increased enzyme activity. The coexistence of TERTp mutations with BRAFV600E is reported in some tumors as papillary thyroid carcinoma or cutaneous melanoma, and it is associated with aggressiveness. Ameloblastoma and AC harbor BRAFV600E, however, it remains unknown whether these odontogenic tumors also show mutations in TERT promoter. Objective: To investigate TERTp hotspot mutations in ameloblastoma and AC. Study Design: Genomic DNA of paraffin-embedded ameloblastomas (n=6) and AC (n=3) were Sanger-sequenced to assess the hotspot mutations C228T and C250T TERTp. Results: None of the samples harbored TERTp mutations. Conclusion: The results suggest that the mutations C228T and C250T in TERT promoter are not a common event in ameloblastoma and AC. Whether other genetic or epigenetic events in TERT promoter play a role in the tumorigenesis of these odontogenic tumors remains to be elucidated. SUPPORT: FAPEMIG PROBIC.