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目的通过在4号染色体寻找杂合缺失区域,为定位、筛选高频杂合缺失区存在的散发性结直肠癌相关肿瘤抑制基因提供依据。方法20个荧光标记的微卫星引物与83例结、直肠癌的肿瘤和正常组织进行聚合酶链反应。微卫星的平均遗传距离是10.4里摩(cmol)。产物进行电泳、扫描及杂合缺失分析,并与临床、病理因素进行相关性检验。结果短臂(4p)、长臂(4q)的平均杂合缺失率为24.25%、28.56%,可见3个最小的高频缺失区域(Region):R1:在D4S405和D4S3013(4p1415.2)之间;R2:在D4S3000和D4S2915位点之间(4q1221.1);R3:在D4S407和D4S2939位点之间(4q2531.1)。D4S1534位点与肝脏转移有关(P<0.05),其余位点与临床病理因素均无显著相关(P>0.05)。结论4号染色体的3个高频杂合缺失区域4p1415.2、4q1221.1、4q2531.1存在散发性结直肠癌发生、发展相关的肿瘤抑制基因。
Objective To find out the heterozygous deletion region on chromosome 4 and provide the basis for localization and screening of the tumor suppressor gene associated with sporadic colorectal cancer in high frequency heterozygous deletion region. Methods Twenty fluorescently labeled microsatellite primers were used for polymerase chain reaction in 83 patients with colorectal cancer and normal tissues. The average genetic distance of microsatellites is 10.4 mol. Products were electrophoresis, scanning and heterozygous deletion analysis, and clinical and pathological factors were tested. Results The average heterozygous deletion rate of short arm (4p) and long arm (4q) was 24.25% and 28.56%, respectively. Three of the smallest high frequency deletion regions were seen: R1: At D4S405 and D4S3013 (4p1415.2) R2: Between D4S3000 and D4S2915 (4q1221.1); R3: Between D4S407 and D4S2939 (4q2531.1). The location of D4S1534 correlated with liver metastasis (P <0.05), and the other sites had no significant correlation with clinicopathological factors (P> 0.05). Conclusion There are three tumor suppressor genes associated with the occurrence and development of sporadic colorectal cancer in 4 high frequency heterozygous deletion region 4p1415.2, 4q1221.1 and 4q2531.1 on chromosome 4.