title: Ameloblastoma Phenotypes Reflected in Distinct Transcriptome Profiles.
abstract: Ameloblastoma is a locally invasive benign neoplasm derived from odontogenic epithelium and presents with diverse phenotypes yet to be characterized molecularly. High recurrence rates of 50-80% with conservative treatment in some sub-types warrants radical surgical resections resulting in high morbidity. The objective of the study was to characterize the transcriptome of ameloblastoma and identify relevant genes and molecular pathways using normal odontogenic tissue (human "dentome") for comparison. Laser capture microdissection was used to obtain neoplastic epithelial tissue from 17 tumors which were examined using the Agilent 44 k whole genome microarray. Ameloblastoma separated into 2 distinct molecular clusters that were associated with pre-secretory ameloblast and odontoblast. Within the pre-secretory cluster, 9/10 of samples were of the follicular type while 6/7 of the samples in the odontoblast cluster were of the plexiform type (p < 0.05). Common pathways altered in both clusters included cell-cycle regulation, inflammatory and MAPkinase pathways, specifically known cancer-driving genes such as TP53 and members of the MAPkinase pathways. The pre-secretory ameloblast cluster exhibited higher activation of inflammatory pathways while the odontoblast cluster showed greater disturbances in transcription regulators. Our results are suggestive of underlying inter-tumor molecular heterogeneity of ameloblastoma sub-types and have implications for the use of tailored treatment.
authors.affiliation: Pediatric Dentistry, School of Dentistry, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.|Faculty of Dentistry, National University of Singapore, Singapore.
authors.forename: Shijia
authors.initials: S
authors.lastname: Hu
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: Pediatric Dentistry, School of Dentistry, University of North Carolina-Chapel Hill, 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: 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, School of Dentistry, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
authors.forename: John Timothy
authors.initials: JT
authors.lastname: Wright
mesh_terms: D000564:Ameloblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016000:Cluster Analysis; D006801:Humans; D061346:Laser Capture Microdissection; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009804:Odontoblasts / Q000166:cytology / Q000378:metabolism; D009808:Odontogenic Tumors / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D012334:RNA, Neoplasm; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D020928:Mitogen-Activated Protein Kinases