Research Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Institute of Dentistry and Oral Sciences, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
Clin Genet. 2021 Apr;99(4):493-502. doi: 10.1111/cge.13892. Epub 2021 Feb 16.
Like all developmental processes, odontogenesis is highly complex and dynamically regulated, with hundreds of genes co-expressed in reciprocal networks. Tooth agenesis (missing one or more/all teeth) is a common human craniofacial anomaly and may be caused by genetic variations and/or environmental factors. Variants in PAX9, MSX1, AXIN2, EDA, EDAR, and WNT10A genes are associated with tooth agenesis. Currently, variants in ATF1, DUSP10, CASC8, IRF6, KDF1, GREM2, LTBP3, and components and regulators of WNT signaling WNT10B, LRP6, DKK, and KREMEN1 are at the forefront of interest. Due to the interconnectedness of the signaling pathways of carcinogenesis and odontogenesis, tooth agenesis could be a suitable marker for early detection of cancer predisposition. Variants in genes associated with tooth agenesis could serve as prognostic or therapeutic targets in cancer. This review aims to summarize existing knowledge of development and clinical genetics of teeth. Concurrently, the review proposes possible approaches for future research in this area, with particular attention to roles in monitoring, early diagnosis and therapy of tumors associated with defective tooth development.
与所有发育过程一样，牙发生过程高度复杂且受到动态调控，数以百计的基因在相互作用的网络中共同表达。牙齿缺失（缺失一颗或多颗/全部牙齿）是一种常见的人类颅面异常，可能由遗传变异和/或环境因素引起。PAX9、MSX1、AXIN2、EDA、EDAR 和 WNT10A 基因的变异与牙齿缺失有关。目前，ATF1、DUSP10、CASC8、IRF6、KDF1、GREM2、LTBP3 以及 WNT 信号通路的组成部分和调节因子 WNT10B、LRP6、DKK 和 KREMEN1 的变异处于研究前沿。由于致癌作用和牙发生的信号通路相互关联，牙齿缺失可能是癌症易感性早期检测的合适标志物。与牙齿缺失相关的基因变异可作为癌症的预后或治疗靶点。本综述旨在总结牙齿发育和临床遗传学的现有知识。同时，该综述提出了该领域未来研究的可能方法，特别关注在监测、早期诊断和治疗与牙齿发育缺陷相关的肿瘤方面的作用。
