非可控性炎症、表观遗传和遗传改变在结直肠癌发生和侵袭过程中的作用

结直肠癌(colorectal carcinoma,CRC)的发生和发展是慢性炎症促进关键基因后天突变累积的过程.炎症促进癌症进化各阶段均受表观遗传和遗传改变所驱动.在癌症信号刺激下,腺瘤通过积累遗传变异逐渐发展成腺癌.新一代测序技术为阐明癌症进化过程中的“驱动”变异和融合基因提供了有效途径,为癌症进化提供了分子证据.腺瘤恶性转化过程中最明确的遗传改变是微卫星不稳定和染色体不稳定性显著增加.研究CRC的进化规律,尤其是研究体细胞变异的主要目的是明确这种变异影响了何种信号途径,而信号途径是目前探索早期CRC的有效干预方式和CRC靶向治疗的关键.

Role of non-resolving inflammation, epigenetic and genetic alterations in carcinogenesis and invasion of colorectal carcinoma

The development and progression of colorectal cancer (CRC) is a process that accumulates the driver somatic mutations elicited by chronic inflammation. Epigenetic modifications and genetic mutations play key roles in the whole evolutionary process of chronic inflammation-induced CRC. Adenoma gradually progresses into adenocarcinoma via accumulating genetic mutations stimulated by cancer promoting stimulations. The next generation sequencing technology provides an effective way to identify the "driver" mutations and fusion genes in the carcinogenesis, providing molecular evidences for cancer evolution. The most significant genetic changes during malignant transformation from adenoma to adenocarcinoma are the significant increases in microsatellite instability and chromosome instability. The main purpose of investigating the evolutionary process of CRC, especially somatic mutations, is to identify the related signaling pathways, which are the key steps to explore early effective intervention strategies and targeted therapies for CRC.