Mutational Signatures in Mandibular Ameloblastoma Correlate with Smoking

Area of Science:

• Oncology
• Genetics
• Oral Pathology

Background:

• Ameloblastoma is a rare odontogenic tumor with poorly understood etiology and risk factors.
• Limited genomic data exists for ameloblastoma, hindering molecular characterization.

Purpose of the Study:

• To investigate the molecular basis and potential risk factors of mandibular ameloblastoma.
• To identify genetic alterations and mutational signatures in ameloblastoma.

Main Methods:

• Whole exome sequencing was performed on 11 mandibular ameloblastoma samples.
• Analysis of mutational signatures, including COSMIC signatures 4 and 29.
• Identification of mutations in key genes such as BRAF, BCOR, and CDC73.

Main Results:

• Two convergent mutational signatures associated with tobacco carcinogens and chewing habits were identified.
• BRAF hotspot mutations (V600E) and significant inter- and intratumor heterogeneity were observed.
• Recurrent mutations in BCOR and CDC73 genes were found, potentially impacting tumorigenesis and recurrence.

Conclusions:

• Tobacco usage is a potential risk factor for ameloblastoma, warranting further investigation.
• Genetic profiling provides insights into ameloblastoma etiology and suggests potential therapeutic targets.
• Findings highlight the need for screening and prevention strategies, particularly in Asian populations.