目的本课题组前期研究对染色体1q31．1-32．1区域进行杂合缺失精细定位，发现D1S413-D1$2622区域存在高频杂合缺失现象，提示可能有抑癌基因的存在。本研究在此基础上，对该区域与散发性结直肠癌发生相关的抑癌基因开展筛选研究。方法构建包含上述区域基因的基因芯片，对19例散发性结直肠癌标本进行基因芯片扫描，并与其临床病理特征进行统计学分析，筛选该区域与结直肠癌相关的未知抑癌基因，然后对筛选出的候选基因采用Real-timePCR进行初步验证。结果根据前期实验结果，通过检索，挑选了25个基因进行散发性结直肠癌相关基因的筛选。结果发现半胱氨酸甘氨酸富集蛋白1（cysteine and glycine-rich protein1，CSRPl）、LMODl、PPPlR12B和CFHL34个基因表达显著下调。这4个基因表达情况与结直肠癌患者的临床病理特征无关。通过生物信息学分析，推测CSRPl基因可能是该区域中与结直肠癌相关的抑癌基因。通过Real-timePCR验证结果也发现CSRPl基因在结直肠癌组织中表达显著下调，与芯片结果相符。结论CSRPl基因可能是一个与结直肠癌发生相关的新的抑癌基因。
Background As a model for both multistep and multipathway carcinogenesis, colorectal neoplastic progression provides paradigms for researching both oncogenes and tumor suppressor genes （TSGs）. However, the mechanism of colorectal cancer （CRC） is not completely understood, and many genes may be involved in the colorectal carcinogenesis. The purpose of this study was to screen for the potential TSGs on chromosome 1q31.1-32.1 in Chinese patients with sporadic colorectal cancer, to explore whether colorectal cancer in the Chinese population has unique genetic alterations and determine whether other putative TSGs exist and contribute to colon carcinogenesis. Methods Six polymorphic microsatellite markers, at a density of approximately one marker in every 1.6 cM, were chosen for refined loss of heterozygosity （LOH） mapping of 1q31.1-32.1. Eighty-three colorectal cancer patients＇ tumor and normal DNA were analyzed via polymerase chain reaction （PCR） for these microsatellite markers. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.1 and Genotype 2.1 software were used for LOH scanning and analysis. On the basis of refined LOH mapping results, we undertook a microarray-based expression screening to identify tumor association genes in 19 of the CRC cases. Results The average LOH frequency of 1q31.1-32.1 was 24.41%, with the highest frequency of 36.73% （18/49） at D1S2622, and the lowest of 16.42% （11/67） at D1S412. A minimal region of frequent deletion was located within a 2 cM genomic segment at D1S413-D1S2622. There was no significant association between LOH of any marker in the studied regions and the clinicopathological data （patient sex, age, tumor size, growth pattern, or Dukes stage）. On the basis of refined mapping results, we chose 25 genes located in the D1S413-D1S2622 （1q31.3-32.1） region and presented a microarray-based high throughput screening approach in 19 sporadic CRC cases to identify candidate CRC related tumor suppressor genes. This study found 4
