基因突变在结直肠癌诊疗及预后中的研究进展

结直肠癌是常见的恶性肿瘤之一,其发病率居全球恶性肿瘤发病率的第三位,死亡率呈逐年上升趋势。中国已成为全球结直肠癌每年新发病例数和死亡病例数最多的国家。对结直肠癌基因突变状态的识别以及对结直肠癌发生发展过程进行精确分类,可实现对患者进行个性化精准治疗的目的,而精准治疗的实现有赖于基因测序技术。目前,二代测序技术(Next generation sequencing,NGS)结合基因捕获技术,集中对研究者感兴趣的候选基因或外显子进行平行测序,极大拓展了对肿瘤特征基因的认识,为发展新的治疗手段和治疗策略奠定了基础。整合癌症基因组数据库IntOgen已明确72个结直肠癌驱动突变基因,包括“TP53”、“KRAS”、“PIK3CA”等;癌基因数据库Cancer Gene Census目前收录的结直肠癌突变基因有59个,包括原癌基因“BRAF”、抑癌基因“SMAD4”等;在线人类孟德尔遗传OMIM数据库已收录55个与结直肠癌相关的体细胞突变基因,包括“SRC”、“APC”等。本文通过26篇国内外文献,对结直肠癌基因突变检测的共识基因进行综述,并总结了与结直肠癌患者临床诊断、分型、预后、治疗等临床病理特征相关的突变基因标志物。

Research progress of gene mutations in the diagnosis, treatment, and prognosis of colorectal cancer

Colorectal cancer is a common malignant tumor, whose incidence ranks third in the global incidence of malignant tumors, and the mortality rate is increasing year by year. China has become the country with the largest number of new cases and deaths of colorectal cancer each year in the world. The identification of colorectal cancer gene mutation status and the precise classification of the occurrence and development of colorectal cancer can achieve personalized and precise treatment of patients, and the realization of precise treatment depends on gene sequencing technology. At present, the next generation sequencing (NGS) combined with gene capture technology focuses on parallel sequencing of candidate genes or exons that researchers are interested in, which greatly expands the understanding of tumor characteristic genes and lays foundation for the development of new treatment strategies. The IntOgen database has identified 72 colorectal cancer driver mutation genes, such as "TP53", "KRAS",and "PIK3CA". The Cancer Gene Census currently includes 59 colorectal cancer mutation genes, including the original oncogene "BRAF",tumor suppressor gene "SMAD4", and so on. The OMIM database has included 55 somatic mutation genes related to colorectal cancer, including "SRC"and "APC". Based on 26 domestic and foreign research studies, this article reviews the consensus genes for colorectal cancer gene mutation detection, and summarizes the mutation gene markers related to the clinical diagnosis, classification, prognosis, treatment, and other clinicopathological characteristics of colorectal cancer patients.