散发性结直肠癌1号染色体1q31.1-32.1区域等位基因杂合缺失精细定位研究

目的 对染色体1q31.1-32.1区域进行杂合缺失(LOH)精细定位分析,探讨更为精确的高频LOH区域并筛选可能与结直肠癌相关的抑癌基因.方法 在1q31.1-32.1区域选择6对微卫星引物与83例结直肠癌的肿瘤和正常组织进行聚合酶链反应(PCR).产物在ABI Prism 377自动荧光测序仪进行电泳,以GeneScan 3.1和Genotyper 2.1软件进行扫描以及LOH分析.LOH结果与临床病理参数之间的关系比较采用χ2检验.结果 1q 31.1-32.1区域平均LOH率是22.98%.以D1S2622位点最高,为36.73%(18/49),最低是D1S412,为16.42%(11/67).结果 显示,更精确的缺失范围定位应该在D1S413和D1S2622之间(1q 31.3-32.1),约2 cM的遗传距离范围内.该区域各位点的LOH率与性别、年龄、肿瘤大小、生长方式以及肿瘤Dukes分期无明显相关.结论 将1q31.1-32.1区域高频等位基因缺失精细定位于D1S413和D1S2622位点之间,遗传学距离约2cM的区域内,提示在该区域存在与结直肠癌发生发展相关的抑癌基因.

Refined mapping of loss of heterzygosity on 1q31. 1-32. 1 in sporadic colorectal carcinoma

Objective To explore preeise loss of heterzygosity (LOH) regions on 1 q31.1-32.1 in Chinese patients with coloreetal cancer. Methods Six fluoreseence-labeled polymorphic markers on 1q31.1-32.1 were chosen. These markers in 83 colorectal cancers and normal tissues were analyzed by PCR. PCR products were electrophoresed for LOH scanning and analysis. Results The average LOH fre-quency of 1q31.1-32.1 was 22.98% ,with the highest frequency of 36.73% (18/49) at D1S2622,and the lowest of 16.42% (11/67) at D1S412 respectively. A minimal region of frequent deletion was located within a 2 cM genomic segment at D1S413-D1S2622 (1q31.3-32.1). There was no signifieant association between LOH of each marker on 1 q31.1-32.1 and the elinieopathologieal data (patients' sex, age, tumor size,growth pattern or Dukes stage). Conclusion Through our detailed deletion mapping,the critical and preeise deleted regions were located within 2 cM chromosome segment encompassing 2 loei ( D1S413, D1S2622).