多种基因按一定的顺序发生突变引起相应蛋白的表达异常导致结肠癌（CRC）发生发展的理论已被许多研究证实，而至今与散发性结直肠癌（sCRC）相关的基因鲜见报道。本项目在前期利用外显子组测序技术对3例中国汉族sCRC患者的肿瘤组织样本测序及分析的基础上，运用新的筛查策略确定肿瘤组织特异的功能缺失（LoF）突变位点，结合样本病理信息、基因生物信息等数据，筛选出候选基因:DDI2。通过对独立样本检测，验证了DDI2的变异位点为低频突变位点，确定其为高可信性候选基因。进一步筛查独立样本中DDI2其他可能的功能性突变位点，并且通过体内外功能实验来验证DDI2及其功能性突变位点参与并影响sCRC发生发展，为sCRC疾病早期诊断及靶向治疗奠定理论基础。

That a large number of gene mutations occured in a certain order lead to abnormal expression of the corresponding protein, which could result in colorectal cancer (CRC), has been proven in many research, but less genes associated with sporadic colorectal cancer (sCRC) have been reported. Using exome sequencing of 3 cases of sCRC samples in the Chinese Han population and new screening strategies to determine the LoF mutations in tumor tissue specificity, combined pathology information and genetically information, we have selected the candidate gene: DDI2. The test of independent samples verified low frequency of DDI2 variation and these samples will be further screened DDI2 other possible LoF mutations. The functional experiments will be designed to certify DDI2 and mutations influence the development of sCRC. This project will lay the foundation of early diagnosis and targeted treatment of sCRC.