Analysis of Oncogene Mutations in Odontogenic Myxoma

Abstract

Odontogenic myxoma (OM) is a rare, benign mesenchymal odontogenic tumor. Presently, the molecular mechanisms underlying OM remain unclear, and no diagnostic markers have been identified. This study aimed to investigate gene mutations related to the MAPK/ERK, PI3K/mTOR, and β-catenin/Wnt pathways in OM, including KRAS, PIK3CA, and CTNNB1, and their associated proteins. Additionally, the association between gene mutations and their associated protein expression was also investigated. DNA was extracted from 11 formalin-fixed, paraffin-embedded OM tissues for PCR. PCR-positive samples using KRAS, PIK3CA, and CTNNB1 primers were sent for DNA sequencing to investigate mutations in KRAS exon 2 codons 12 and 13, PIK3CA exon 9 codons 542 to 549, and CTNNB1 exon 3 codons 32 to 45. Proteins associated with these pathways, including p-ERK1/2, p-mTOR, and β-catenin, were examined using immunohistochemistry. We found that 2 of 11 cases (18.18%) had KRAS mutation (G12V), with almost all cases (90.91%) expressing p-ERK1/2 in the spindle-shaped tumor cells. Only 1 of 9 cases (11.11%) possessed PIK3CA mutation (Q546E), although all cases variably expressed p-mTOR in the tumor cells. None of the case showed CTNNB1 mutation and β-catenin expression. Statistical analysis indicated no significant association between gene mutations and their associated proteins in OM (P > .05). In conclusion, the presence of KRAS and PIK3CA mutations, along with p-ERK1/2 and p-mTOR expression in a subset of OM, suggests that the pathogenesis of this tumor may involve the MAPK/ERK and PI3K/mTOR signaling pathways. In contrast, the absence of CTNNB1 mutations and β-catenin expression indicates no association between OM pathogenesis and the β-catenin/Wnt signaling pathway. However, further studies with larger sample sizes are needed to confirm these findings.