Transcriptome Variability in Keratocystic Odontogenic Tumor Suggests Distinct Molecular Subtypes

Abstract

Keratocystic Odontogenic Tumor (KCOT) is a locally aggressive developmental cystic neoplasm thought to arise from the odontogenic epithelium. A high recurrence rate of up to 30% has been found following conservative treatment. Aggressive tumor resection can lead to the need for extensive reconstructive surgery, resulting in significant morbidity and impacting quality of life. Most research has focused on candidate-genes with a handful of studies employing whole transcriptome approaches. There is also the question of which reference tissue is most biologically-relevant. This study characterizes the transcriptome of KCOT using whole genome microarray and compare it with gene expression of different odontogenic tissues (“dentome”). Laser capture microdissection was used to isolate the neoplastic epithelial tissue in 20 cases. KCOT gene expression was compared with the “dentome” and relevant pathways were examined. Cluster analysis revealed 2 distinct molecular subtypes of KCOT. Several inflammatory pathways were activated in both subtypes. The AKT pathway was activated in one subtype while MAP kinase pathway was activated in the other. Additionally, PTCH1 expression was downregulated in both clusters suggesting involvement in KCOT tumorigenesis. In conclusion, this study provides new insights into the transcriptome of KCOT and highlights pathways that could be of diagnostic and prognostic value.

Molecular alterations in odontogenic keratocysts as potential therapeutic targets

“…Based on their results, the authors confirmed that ameloblastomas and OKCs are distinct lesions, and according to the gene expression profile of ameloblastomas, these lesions are more similar to the dental lamina, while gene expression in OKCs indicates differentiation toward keratinocytes . Recently, microdissected OKC epithelial tissue from 20 sporadic cases was included in transcriptome analysis via whole‐genome microarray . The authors reported that PTCH1 and GLI were downregulated.…”

“…30 Recently, microdissected OKC epithelial tissue from 20 sporadic cases was included in transcriptome analysis via whole-genome microarray. 31 The authors reported that PTCH1 and GLI were downregulated. This last finding is in contrast with previous studies that used OKCs, medulloblastomas and skin tumors, which showed PTCH1 loss and GLI1 overexpression instead of downregulation.…”

Estimulação Óssea Através De Ultrasson

“…Quanto a análise comparativa direta entre os cimentos AH Plus e Sealer Plus, que possuem composição química semelhante, o resultado dos testes apresentou que o AH Plus possui diâmetro médio de escoamento maior do que o Sealer Plus, como corrobora o estudo realizado por Vertuan et al (2016).…”

Exploring the potential of laser capture microdissection technology in integrated oral biosciences

“…Hu et al () compared the transcriptome of KCOT utilizing whole‐genome microarray with the ‘dentome’ and identified two different molecular subtypes operative in non‐syndromic KCOTs. In one molecular subtype, the phosphoinositide 3‐kinase/AK strain transforming (PI3K/AKT) pathway was functional, and in the other, mitogen‐activated protein kinase (MAPK) pathway was active.…”

“…The former has a gene expression profile similar to secretory ameloblast (s‐KCOT), while the latter had a gene expression profile resembling odontoblast (o‐KCOT). The common downregulated genes in these distinct molecular subtypes were PCTH‐1 and GLI‐1 (Hu et al , ). The authors concluded that even though the phenotype was same (both were KCOT), yet their response to therapy may be different (based on molecular pathway operative, i.e., their genotypes were different).…”