title: 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.
authors.affiliation: Pediatric Dentistry, University of North Carolina, Chapel Hill, NC, USA.|Faculty of Dentistry, National University of Singapore, Singapore.
authors.forename: Shijia
authors.initials: S
authors.lastname: Hu
authors.affiliation: Pediatric Dentistry, University of North Carolina, Chapel Hill, NC, USA.|Epidemiology, Gillings School of Global Public Health, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Kimon
authors.initials: K
authors.lastname: Divaris
authors.affiliation: Cancer Genetics, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Parker
authors.affiliation: Diagnostic Sciences, School of Dentistry, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Padilla
authors.affiliation: Diagnostic Sciences, School of Dentistry, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Murrah
authors.affiliation: Pediatric Dentistry, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: John Timothy
authors.initials: JT
authors.lastname: Wright
mesh_terms: D016000:Cluster Analysis; D004848:Epithelium / Q000473:pathology; D005838:Genotype; D006651:Histocytochemistry; D006801:Humans; D061346:Laser Capture Microdissection; D046228:Microarray Analysis; D008853:Microscopy; D009808:Odontogenic Tumors / Q000145:classification / Q000473:pathology*; D059467:Transcriptome