Discovery of novel molecular characteristics and cellular biological properties in ameloblastoma.

Cancer Med 2020 Apr 25;9(8):2904-2917. Epub 2020 Feb 25.

Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Nagakute, Japan.

Ameloblastoma is a rare odontogenic benign tumor accounting for less than 1% of head and neck tumors. Advanced next generation sequencing (NGS) analyses identified high frequency of BRAF V600E and SMO L412F mutations in ameloblastoma. Despite the existence of whole genomic sequence information from patients with ameloblastoma, entire molecular signature of and the characteristics of ameloblastoma cells are still obscure. In this study, we sought to uncover the molecular basis of ameloblastoma and to determine the cellular phenotype of ameloblastoma cells with BRAF mutations. Our comparative cDNA microarray analysis and gene set enrichment analysis (GSEA) showed that ameloblastoma exhibited a distinct gene expression pattern from the normal tissues: KRAS-responsive gene set is significantly activated in ameloblastoma. Importantly, insulin like growth factor 2 (IGF2), a member of KRAS-responsive genes, enhances the proliferation of an ameloblastoma cell line AMU-AM1 with BRAF mutation. In addition, Toll-like receptor 2 (TLR2) knockdown readily inactivated KRAS-responsive gene sets as well as increases caspase activities, suggesting that TLR2 signaling may mediate cell survival signaling in ameloblastoma cells. Collectively, the findings may help to further clarify the pathophysiology of ameloblastoma and lead to the development of precision medicine for patients with ameloblastoma.

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Source
http://dx.doi.org/10.1002/cam4.2931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163100PMC
April 2020

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References

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Clinicopathological study of 100 Nigerian cases of ameloblastoma
Odukoya O et al.
Niger Postgrad Med J 2008

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