Early Dental Epithelial Transcription Factors Distinguish Ameloblastoma from Keratocystic Odontogenic Tumor

被引:94
作者
Heikinheimo, K. [1 ,2 ,3 ,4 ]
Kurppa, K. J. [5 ,6 ]
Laiho, A. [7 ,8 ]
Peltonen, S. [2 ,9 ]
Berdal, A. [10 ]
Bouattour, A. [11 ]
Ruhin, B. [10 ,12 ]
Caton, J. [13 ]
Thesleff, I. [14 ]
Leivo, I. [2 ,15 ]
Morgan, P. R. [13 ]
机构
[1] Univ Turku, Inst Dent, Dept Oral & Maxillofacial Surg, FI-20520 Turku, Finland
[2] Turku Univ Hosp, FIN-20520 Turku, Finland
[3] Univ Eastern Finland, Inst Dent, Dept Oral Diagnost Sci, Kuopio, Finland
[4] Kuopio Univ Hosp, Dept Oral & Maxillofacial Dis, SF-70210 Kuopio, Finland
[5] Univ Turku, Dept Med Biochem & Genet, FI-20520 Turku, Finland
[6] Turku Doctoral Programme Mol Med, Turku, Finland
[7] Univ Turku, Turku Ctr Biotechnol, Microarray & Sequencing Ctr, FI-20520 Turku, Finland
[8] Abo Akad Univ, Turku, Finland
[9] Univ Turku, Dept Dermatol, FI-20520 Turku, Finland
[10] Univ Paris 07, Inst Biomed Cordeliers, INSERM UMRS 872, Paris, France
[11] Andre Gregoire Hosp, Dept Maxillofacial Surg & Stomatol, Paris, France
[12] Hop La Pitie Salpetriere, AP HP, Dept Maxillofacial Surg & Stomatol, Paris, France
[13] Kings Coll London, Inst Dent, London WC2R 2LS, England
[14] Univ Helsinki, Inst Biotechnol, Helsinki, Finland
[15] Univ Turku, Dept Pathol, FI-20520 Turku, Finland
关键词
dental lamina; epithelial stem cell; gene expression; keratocystic odontogenic tumor; tooth germ; tumor bioinformatics; HORMONE-RELATED PROTEIN; BENIGN CYSTIC NEOPLASM; TOOTH DEVELOPMENT; AGGRESSIVE NATURE; CELL CARCINOMA; GENE-EXPRESSION; MUTATIONS; IDENTIFICATION; PROLIFERATION; REGENERATION;
D O I
10.1177/0022034514556815
中图分类号
R78 [口腔科学];
学科分类号
1003 ;
摘要
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.
引用
收藏
页码:101 / 111
页数:11
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