体细胞突变在自身炎症及免疫性疾病发生中的作用

The somatic mutations in autoinflammatory and autoimmune diseases

不同于由遗传获得的生殖系突变,体细胞突变是受精卵形成后在细胞中新出现的突变。体细胞突变由多种内外源刺激引起,并受到微环境、基因功能、个体发育时序等因素影响,具有发生于生命周期各个阶段,随机性和多样性的特点。体细胞突变在肿瘤发生中的作用已得到公认,而近年来发生于免疫细胞的体细胞突变引发的免疫相关疾病开始受到人们的关注。本文回顾了体细胞突变发生的分子机制,及其引发自身炎症与免疫性疾病的研究进展,旨在强调体细胞突变在基因功能异常相关疾病发生、诊断和治疗中的意义。

Somatic mutations are de novo mutations occur after zygogenesis,which are distinguished from germline mutations by nonhereditary acquisition.Somatic mutations are caused by multiple internal and external stimuli,and are influenced by microenvironment,gene functions,and developmental timing,hence the characteristics of various and random.Whereas the role of somatic mutations in malignant proliferative diseases is long-recognized,growing evidence of somatic variants in immune cells in nonmalignant immune-related disorders has been no focus since recent years.We reviewed the molecular mechanisms underlying somatic mutations and its recent progress in autoinflammatory and autoimmune diseases,for the purpose of emphasizing the significance of somatic mutations in the diagnosis and treatment of diseases related to dysregulated gene functions.