Amm Hope M, MacDougall Mary
Institute of Oral Health Research, University of Alabama at Birmingham School of Dentistry, Birmingham, AL 35294, USA.
Curr Oral Health Rep. 2016 Jun;3(2):82-92. doi: 10.1007/s40496-016-0085-z. Epub 2016 Mar 31.
Several molecular pathways have been shown to play critical roles in the pathogenesis of odontogenic tumors. These neoplasms arise from the epithelial or mesenchymal cells of the dental apparatus in the jaw or oral mucosa. Next generation genomic sequencing has identified gene mutations or single nucleotide polymorphisms associated with many of these tumors. In this review, we focus on two of the most common odontogenic tumor subtypes: ameloblastoma and keratocystic odontogenic tumors. We highlight gene expression and protein immunohistological findings and known genetic alterations in the hedgehog, BRAF/Ras/MAPK, epidermal growth factor receptor, Wnt and Akt signaling pathways relevant to these tumors. These various pathways are explored to potentially target odontogenic tumors cells and prevent growth and recurrence of disease. Through an understanding of these signaling pathways and their crosstalk, molecular diagnostics may emerge as well as the ability to exploit identified molecular differences to develop novel molecular therapeutics for the treatment of odontogenic tumors.
几种分子途径已被证明在牙源性肿瘤的发病机制中起关键作用。这些肿瘤起源于颌骨或口腔黏膜中牙器官的上皮或间充质细胞。新一代基因组测序已鉴定出与许多此类肿瘤相关的基因突变或单核苷酸多态性。在本综述中,我们重点关注两种最常见的牙源性肿瘤亚型:成釉细胞瘤和牙源性角化囊性瘤。我们强调基因表达、蛋白质免疫组织学发现以及与这些肿瘤相关的刺猬信号通路、BRAF/Ras/MAPK、表皮生长因子受体、Wnt和Akt信号通路中已知的基因改变。探索这些不同的途径以潜在地靶向牙源性肿瘤细胞并预防疾病的生长和复发。通过了解这些信号通路及其相互作用,分子诊断可能会出现,同时也有能力利用已确定的分子差异开发用于治疗牙源性肿瘤的新型分子疗法。