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International Poster Journal of Dentistry and Oral Medicine
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Int Poster J Dent Oral Med 13 (2011), No. 1     15. Mar. 2011

Int Poster J Dent Oral Med 2011, Vol 13 No 1, Poster 520

Odontogenic tumors – a saga of its genesis

Language: English
 

Authors:
Dr. Juhi Verma Upadhyay, Senior lecturer Dr. Ram Ballabh Upadhyay,
Department of Oral and Maxillofacial Pathology, KD Dental College and Hospital Mathura, Uttar Pradesh, India
Prof. Dr. Nirmala N. Rao,
Department of Oral and Maxillofacial Pathology, Manipal College of Dental Sciences, Manipal, Karnataka, India

Date/Event/Venue:
December 26-28, 2008
XVII National Conference of IAOMP
Kolkata, India
 

The earliest reports on odontogenic tumors date back to 1839 and in spite of researches over the decades the etiology and pathogenesis of this distinct group of jaw lesions is still incompletely understood. It is well established that odontogenic tumors arise from the epithelial and/or mesenchymal elements of the tooth forming apparatus and along with epithelial-mesenchymal interactions there are molecular and genetic alterations associated with the development and progression of odontogenic tumors (figure 1). Odonogenesis is a complex process which involves the interplay of several genes, growth factors, signalling molecules, transcription factors and, intra- and extra- cellular molecules (figure 2). Any aberrancy in this process is likely to lead to malignancy. It would not be wrong to agree that as the tooth develops though various stages, any dental follicle lost in the path of odontogenesis could give rise to variants of odontogeneic tumors (figure 3) with progressive development of odontogenic derivatives. These dental follicles could be un-erupted third molars, aberrant follicles, and/or supernumerary tooth germs. There are several genes which on aberrant expression may lead to arrest of odontogenesis at that particular stage (Figure 4). Anomalies like anodontia/oligodontia may result from defects in expression of Msx1, Lef1, BCOR, whereas supernumerary teeth with permanent dentition may be due to RUNX2 and trichodentoosseous syndrome results from Dlx3, all of which may be a potential source of odontogenic tissues. Also recently it has been proposed that various tumerogenic factors (initiators) and tumor promoting factors (supporters) all play a role in synchrony towards the genesis of odontogenic tumors(Table-1). It is important to understand that the odontogenic tumors arise from the odontogenic apparatus and the complex process involves several stages and factors. Thus we intend to outline the multi-step etiology and draw the future attention towards better understanding of odontogenic tumors.

Fig. 1: Various histogenic sources for odontogenic tumors. Fig. 2: Stages of odontogenesis, with expression of various genes and growth factors for each stage.
Fig. 3: Variants of odontogenic tumors Fig. 4: Arrest of tooth development at bud to bell stage if corresponding genes are expressed aberrantly
TUMOR INITIATORS
Oncogenes- RAS, Cmyc, Fos Dysregulation of cell proliferation
Tumor suppressor genes- p53 cell cycle arrest
APC regulates Wnt pathway
RTB cell proliferation
Regulators of tooth development SHH signalling cell to cell interaction, cell proliferation, Epithelial Mesenchymal interaction
Wnt signalling nuclear accumulation of β-catenin
Oncogenes EBV, HPV  
Hard tissue related proteins bone sialoproteins, amelogenin tumor development and progression; associated with pathologic mineralization
BMP-2, -4, -7  
Growth factors TGF-α,-β, FGF -1,-2 Tumor growth and invasion
HGF Cell differentiaton
Telomerase   cell immortality
Cell cycle regulators cyclin D1, p61, p21, p27 Uncontrolled cellular division
Apoptosis related factors Bcl-2, IAP, Fas, TNF-α, p53 Prolonged cell survival
TUMOR SUPPORTERS
Cell adhesion molecules E-selectin, ICAM-1, VCAM-1, E-cadherin, Integrin, CD44 Aid in tumor invasion and survival
Matrix degrading proteinases MMP-1,-1,-1/ TIMP-1,-2, Heparanase  
Angiogenic factors VEGF  
Osteolytic cytokines IL-1, -6, TNF-α, PTHrP, RANKL/OPG
Table 1: Tumor initiators and tumor supporters in pathogenesis of odontogenic tumors
 

Literature

  1. Stolf DP et al,Genetic aspects of Ameloblatoma, Biotechnol.Mol. Biol.Rev 2007; 2(5);116-122.
  2. Matalova E et al. tooth Agenesis: from Molecular Geneticsto Molecular Dentistry, J Dent Res2008: 87(7);617-623.
  3. Kumamoto H. molecular pathology of Odontogenic tumors, J oral Pathol Med, 2006: 35; 65-74.
  4. Eversole LR et al. Histogenesis of odontogenic tumors, Oral Surg,1971: 22(4); 569-581.
     

This Poster was submitted by Dr. Juhi Verma Upadhyay.
 

Correspondence address:
Dr. Ram Ballabh Upadhyay
K. D. Dental College and Hospital, Mathura
Department of Oral Pathology
Mathura-Delhi National Highway # 2
Mathura - 281006
Uttar Pradesh, India