消化系统非癌组织细胞突变的意义及研究进展

Significance and progress of mutations in non-tumorous esophageal,colorectal and liver tissues

体细胞突变随着机体衰老而不断积累,进而驱动癌症的发生发展,而慢性炎症、诱变剂暴露等因素则大大加速该过程。描绘并理解非癌组织细胞如何累积和选择这些突变,对于认识癌症的发生发展过程至关重要,但目前人们在这方面的认识仍非常有限。借助近年来快速发展的高通量高深度二代测序技术,人们得以逐渐清晰地认识非癌组织细胞中的突变累积及克隆演进动力学。非癌组织细胞中的突变具有广泛性、克隆性、选择性,既有可能影响肿瘤发生,也有部分突变利于组织修复及再生。这些研究成果加深了人们对非癌组织细胞突变导致组织稳态失衡及肿瘤发生的认识,为探究癌症的起源提供了新的方向和思路。在此,本文对更新活跃、易于突变累积的消化系统器官(食管、结直肠、肝脏组织)在本领域的研究进展进行综述,以丰富本问题的认知。

Somatic mutations accumulate with the aging of organism and drive tumorigenesis,which could be accelerated by chronic inflammation and mutagenic reagents exposure.However,it is difficult to completely delineate the accumulating and selecting process of mutations in non-tumorous cells.With the rapid development of high-throughput and high-depth next-generation sequencing technologies in recent years,mutation accumulation and cloning evolution in non-tumorous tissue cells have been gradually understood.Mutations in non-tumorous tissue are widespread,clonal and selective,which could promote tumorigenesis or facilitate tissue repair and regeneration.Such progress shed light on the homeostasis imbalance and tumorigenesis caused by cell mutations in non-cancer tissues,thus to provide new insights for further research.Here,we reviewed the research progress of this area in rapid-regenerating,easily-accumulating digestive system organs(esophagus,colorectal and liver),thereby providing better understanding of non-tumorous tissue mutation.