Early dental epithelial transcription factors distinguish ameloblastoma from keratocystic odontogenic tumor.
The aim of the study was to characterize the molecular relationship between ameloblastoma and keratocystic odontogenic tumor (KCOT) by means of a genome-wide expression analysis. Total RNA from 27 fresh tumor samples of 15 solid/multicystic intraosseous ameloblastomas and 12 sporadic KCOTs was hybridized on Affymetrix whole genome arrays. Hierarchical clustering separated ameloblastomas and KCOTs into 2 distinct groups. The gene set enrichment analysis based on 303 dental genes showed a similar separation of ameloblastomas and KCOTs. Early dental epithelial markers PITX2, MSX2, DLX2, RUNX1, and ISL1 were differentially overexpressed in ameloblastoma, indicating its dental identity. Also, PTHLH, a hormone involved in tooth eruption and invasive growth, was one of the most differentially upregulated genes in ameloblastoma. The most differentially overexpressed genes in KCOT were squamous epithelial differentiation markers SPRR1A, KRTDAP, and KRT4, as well as DSG1, a component of desmosomal cell-cell junctions. Additonally, the epithelial stem cell marker SOX2 was significantly upregulated in KCOT when compared with ameloblastoma. Taken together, the gene expression profile of ameloblastoma reflects differentiation from dental lamina toward the cap/bell stage of tooth development, as indicated by dental epithelium-specific transcription factors. In contrast, gene expression of KCOT indicates differentiation toward keratinocytes.
Department of Oral and Maxillofacial Surgery, Institute of Dentistry, University of Turku, Turku, Finland Turku University Hospital, Turku, Finland Department of Oral Diagnostic Sciences, Institute of Dentistry, University of Eastern Finland, Kuopio, Finland Department of Oral and Maxillofacial Diseases, Kuopio University Hospital, Kuopio, Finland krihei@utu.fi.
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Heikinheimo
Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland Turku Doctoral Programme of Molecular Medicine, Turku, Finland.
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Kurppa
Microarray and Sequencing Centre, Turku Centre for Biotechnology, University of Turku, Turku, Finland Åbo Akademi University, Turku, Finland.
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Laiho
Turku University Hospital, Turku, Finland Department of Dermatology, University of Turku, Turku, Finland.
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Peltonen
Molecular Oral Pathophysiology, INSERM UMRS 872, Cordeliers Biomedical Institute, Paris 7 University, Paris, France.
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Berdal
Department of Maxillofacial Surgery and Stomatology, André Grégoire Hospital, Paris, France.
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Bouattour
Molecular Oral Pathophysiology, INSERM UMRS 872, Cordeliers Biomedical Institute, Paris 7 University, Paris, France Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Department of Maxillofacial Surgery and Stomatology, Paris, France.
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Ruhin
Head and Neck/Oral Pathology, Dental Institute, King's College London, London, UK.
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J
Catón
Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
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Thesleff
Turku University Hospital, Turku, Finland Department of Pathology, University of Turku, Turku, Finland.
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Leivo
Head and Neck/Oral Pathology, Dental Institute, King's College London, London, UK.
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Morgan
D000564:Ameloblastoma / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics; D051183:Desmoglein 1 / Q000235:genetics; D004848:Epithelium / Q000737:chemistry; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D053527:Keratin-4 / Q000235:genetics; D015603:Keratinocytes / Q000502:physiology; D060850:LIM-Homeodomain Proteins / Q000235:genetics; D005810:Multigene Family / Q000235:genetics; D009808:Odontogenic Tumors / Q000235:genetics*; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics; D014083:Tooth Germ / Q000737:chemistry*; D014157:Transcription Factors / Q000235:genetics*; D000097577:Homeobox Protein PITX2
D050676:Core Binding Factor Alpha 2 Subunit; D055233:Cornified Envelope Proline-Rich Proteins; D051183:Desmoglein 1; D018398:Homeodomain Proteins; D053527:Keratin-4; D060850:LIM-Homeodomain Proteins; D044162:Parathyroid Hormone-Related Protein; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C495297:DSG1 protein, human; C088334:Distal-less homeobox proteins; C084119:MSX2 protein; C470121:PTHLH protein, human; C493728:RUNX1 protein, human; C527782:SOX2 protein, human; C524531:SPRR1A protein, human; C063843:insulin gene enhancer binding protein Isl-1
dental lamina; epithelial stem cell; gene expression; keratocystic odontogenic tumor; tooth germ; tumor bioinformatics