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基于肿瘤发生和牙发生的原发性牙源性肿瘤发病机制。

Pathogenesis of primordial odontogenic tumour based on tumourigenesis and odontogenesis.

机构信息

Division of Anatomical and Cellular Pathology, Department of Pathology, Iwate Medical University, Yahaba Shiwa-gun, Japan.

Molecular Pathology Area, Faculty of Dentistry, Universidad de la República, Montevideo, Uruguay.

出版信息

Oral Dis. 2018 Oct;24(7):1226-1234. doi: 10.1111/odi.12914. Epub 2018 Jul 10.

Abstract

OBJECTIVE

Primordial odontogenic tumour (POT) is a rare benign mixed epithelial and mesenchymal odontogenic tumour. POT is composed of dental papilla-like tissue covered with cuboidal to columnar epithelium that resembles to inner and outer enamel epithelium of the enamel organ without dental hard tissue formation. The aim of this study was to examine pathogenesis of POT based on tumourigenesis and odontogenesis.

SUBJECTS AND METHODS

Six cases of POT were submitted for study. DNA analysis and transcriptome analysis were performed by next-generation sequencing. Expression of amelogenin, ameloblastin and dentin sialophosphoprotein (DSPP) was examined by immunohistochemistry.

RESULTS

There were no gene mutations detected in any of analysed 151 cancer- and 42 odontogenesis-associated genes. Enamel protein-coding genes of Amelx, Ambn and Enam, and dentin protein-coding genes of Col1a1, Dspp, Nes and Dmp1 were expressed, whereas expression of dentinogenesis-associated genes of Bglap, Ibsp and Nfic was negative or very weak suggesting inhibition of dentin formation in POT after odontoblast differentiation. Immunoreactivity of amelogenin, ameloblastin and DSPP was detected in POT.

CONCLUSIONS

Pathogenesis of POT is considered to be genetically different from other odontogenic tumours. It is suggested that inhibition of enamel and dentin formation in POT is due to defects in dentin formation process.

摘要

目的

原始牙源性肿瘤(POT)是一种罕见的良性混合上皮和间叶性牙源性肿瘤。POT 由类似于釉器内、外釉上皮的牙乳头样组织组成,覆盖有立方状至柱状上皮,但无牙体硬组织形成。本研究旨在基于肿瘤发生和牙发生来研究 POT 的发病机制。

对象和方法

提交了 6 例 POT 病例进行研究。通过下一代测序进行 DNA 分析和转录组分析。通过免疫组织化学检查釉原蛋白、釉基质蛋白和牙本质涎磷蛋白(DSPP)的表达。

结果

在分析的 151 个癌症相关基因和 42 个牙发生相关基因中均未检测到基因突变。Amelx、Ambn 和 Enam 的釉蛋白编码基因,Col1a1、DspP、Nes 和 Dmp1 的牙本质蛋白编码基因表达,而牙本质发生相关基因 Bglap、Ibsp 和 Nfic 的表达为阴性或非常弱,表明在牙源性分化后 POT 中的牙本质形成受到抑制。POT 中检测到釉原蛋白、釉基质蛋白和 DSPP 的免疫反应性。

结论

POT 的发病机制被认为与其他牙源性肿瘤在基因上不同。提示 POT 中釉质和牙本质形成的抑制是由于牙本质形成过程中的缺陷所致。

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