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目的抑癌基因的杂合缺失(LOH)被认为是结直肠癌形成的通路之一。本实验通过对1号染色体1p36.33～36.31、1q31.1～32.1区域进行杂合缺失精细定位分析,以发现更精确的高频杂合缺失区域。方法在1p36.33～36.31、1q31.1～32.1区域分别选择7个、6个荧光标记微卫星引物与83例结直肠癌的肿瘤和正常组织进行聚合酶链反应(PCR)反应。产物在电泳后进行LOH分析。LOH结果与临床病理参数之间的关系比较采用x~2检验。结果1p36.33～36.31区域平均杂合缺失率是31.47%,以D1S243位点最高,为47.22%(34/72),最低是D1S1347,为7.35% (5/68)。存在两个高频杂合缺失区域:D1S243位点(1p36.33)以及D1S468-D1S2660区域(1p36.32～36.31)。1q31.1～32.1区域平均杂合缺失率是22.98%,以D1S2622位点最高,为36.73%(18/49),最低是D1S412,为16.42%(11/67)。更精确的缺失范围定位在D1S413和D1S2622之间(1q31.3～32.1),大约2cm的遗传距离范围内。1p36.33～36.31、1q31.1～32.1区域各位点的杂合缺失率与性别、年龄、肿瘤大小、生长方式以及Dukes分期无显著相关。提示该区域上的杂合缺失现象普遍存在于各种类型的散发性结直肠癌中。结论1号染色体上存在3个高频杂合缺失区域,D1S243位点(1cm)、D1S468和D1S2660位点之间(3cm)以及D1S413和D1S2622之间(2cm),提示在这些区域存在与结直肠癌相关的抑癌基因。
Purpose The heterozygous deletion of tumor suppressor gene (LOH) is considered as one of the pathways of colorectal cancer formation. In this experiment, the heterozygous deletion precise mapping of chromosome 1p36.33 ~ 36.31 and 1q31.1 ~ 32.1 was carried out to find a more precise high frequency heterozygous deletion region. Methods Seven (1) PCR products were selected from 1p36.33 ~ 36.31 and 1q31.1 ~ 32.1, respectively. Six microsatellite primers were used to detect the tumor and normal tissues of 83 patients with colorectal cancer by polymerase chain reaction (PCR). The product was subjected to LOH analysis after electrophoresis. LOH results and clinicopathological parameters were compared using x ~ 2 test. Results The average heterozygous deletion rate in 1p36.33 ~ 36.31 region was 31.47%. The highest D1S243 locus was 47.22% (34/72) and the lowest was D1S1347 (7.35%, 5/68). There are two high frequency heterozygous deletion regions: D1S243 (1p36.33) and D1S468-D1S2660 (1p36.32 ~ 36.31). The average heterozygous deletion rate of 1q31.1 ~ 32.1 region was 22.98%. The highest D1S2622 locus was 36.73% (18/49) and the lowest was D1S412 (16.42%, 11/67). A more accurate deletion range is located within the genetic distance of about 2 cm between D1S413 and D1S2622 (1q31.3 to 32.1). The heterozygous deletions at 1p36.33 ~ 36.31,1q31.1 ~ 32.1 were not significantly associated with gender, age, tumor size, growth pattern and Dukes stage. It is suggested that heterozygous deletion in this region is common in various types of sporadic colorectal cancer. Conclusions There are three high frequency heterozygous deletion regions on chromosome 1. The D1S243 locus (1cm), D1S468 and D1S2660 loci (3cm) and D1S413 and D1S2622 (2cm) Cancer related tumor suppressor genes.