体细胞变异对神经系统常见肿瘤和发育异常类疾病的致病性

The pathogenicity of somatic mutation to common tumors and developmental malformation of the nervous system

在生物体发育过程中各种内源性及外源性因素均可造成DNA损伤,引起体细胞变异。研究表明体细胞变异对肿瘤具有致病性作用,而体细胞变异对神经系统发育异常类疾病的致病性鲜有报道。新一代测序技术的发展,尤其是全外显子测序、靶向深度测序的应用大大提高了低频体细胞变异检出的敏感性,使科研人员重新认识了体细胞变异在神经系统肿瘤和发育异常类疾病发生中的致病性。本文综述了体细胞变异在神经系统肿瘤和发育异常类疾病致病性方面的研究进展,旨在为今后研究该类疾病的遗传病因提供新的思路,同时也为新药开发提供理论依据。

In the course of development, both endogenous and exogenous factors can cause DNA damage, which resulted in somatic mutations. It is recongnized that somatic mutations are the causation of many nervous cancers, the pathogenicity of somatic mutation in developmental malformation of nervous system is unknown yet. With the development of next generation sequencing（NGS）, especially the clinical application of the whole-exome sequencing and the targeted massively parallel sequencing, the somatic mutations with low levels can be detected precisely. The detection of low-level and tissue-specific somatic mutation in patients enables researchers to re-recognize the contribution of somatic mutation to neurological disorders. In this review, we systematically summarize the pathogenicity and characteristics of the somatic mutations in the common tumors and developmental malformation of nervous system, and the new technologies to detect somat-ic mutation in order to extend our understanding of its genetic etiologies and identifying the new drug targets in the future.