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• W4220741582 endingPage "490" @default.
• W4220741582 startingPage "481" @default.
• W4220741582 abstract "Although several types of odontogenic tumors share the same mutations in MAPK pathway genes, their effects on MAPK activation remain unclarified. This study aimed to evaluate the associations between these mutations and ERK phosphorylation in ameloblastoma and mixed odontogenic tumors (MOTs) and to analyze the expression pattern of phosphorylated ERK (p-ERK) for determining the involvement of MAPK activation in the development and progression of odontogenic tumors. Forty-three odontogenic tumors consisting of 18 ameloblastomas and 25 MOTs were analyzed for BRAF, KRAS, and NRAS mutations by Sanger sequencing. The expressions of BRAFV600E protein and p-ERK were detected by immunohistochemistry. The associations between mutation status and p-ERK expression were statistically analyzed. The effect of BRAFV600E inhibition on MAPK activation was investigated in ameloblastoma cells. In benign MOTs, BRAFV600E mutations were neither expressed at the protein level nor associated with p-ERK expression. In contrast, BRAFV600E -mutant ameloblastic fibrosarcoma showed co-expression of BRAF V600E protein and p-ERK, especially in the sarcomatous component. In ameloblastoma, p-ERK was predominantly expressed in the tumor periphery showing a significant correlation with BRAFV600E mutations, and in vitro BRAFV600E inhibition decreased ERK phosphorylation. KRASG12C mutations, previously unidentified in odontogenic tumors, were detected in one case each of benign MOT and ameloblastoma; only the latter was high-p-ERK. In conclusion, unlike in benign MOTs, BRAFV600E and KRASG12C mutations lead to MAPK activation in ameloblastoma, suggesting their role as therapeutic targets. p-ERK intratumoral heterogeneity indicates that MAPK pathway activation may be associated with sarcomatous proliferation of ameloblastic fibrosarcoma and infiltrative behavior of ameloblastoma." @default.
• W4220741582 created "2022-04-03" @default.
• W4220741582 creator A5009471318 @default.
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• W4220741582 date "2022-04-06" @default.
• W4220741582 modified "2023-10-17" @default.
• W4220741582 title "<scp>BRAF V600E</scp> and previously unidentified <scp>KRAS G12C</scp> mutations in odontogenic tumors may affect <scp>MAPK</scp> activation differently depending on tumor type" @default.
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• W4220741582 doi "https://doi.org/10.1002/gcc.23040" @default.
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