胃癌17号染色体抑癌基因候选区域精细定位分析

摘要

Objective To explore precise deleted regions on chromosome 17 and screen the candidate tumor suppressor genes (TSGs) related to gastric carcinoma.Methods Thirteen microsatellite loci on chromosome 17 were chosen.These polymorphic microsatellite markers in 48 cases of gastric cancer were analyzed by using polymerase chain reaction (PCR).PCR products were electrophoresed on an ABI 3730 DNA sequencer.Genemapper 3.2 software was used for loss of heterozygosity (LOH) scanning and analysis.Comparison between LOH frequency and clinicopathological factors was performed by fisher' s exact test.Results Chromosome 17 exhibited higher LOH frequency in gastric carcinoma (31％).There were no valid data on loci of D17S2196,D17S808 and D17S1853.The highest LOH frequency of 48％ (10/21) was seen at D17S796,and the lowest of 20％ (6/30) at D17S956,respectively.Associations between LOH and clinical information revealed that D17S956 and D17S805 were associated with pTNM stage,and D17S831 and D17S921 with differentiation stage.Three refined regiom (D17S1857-D17S805,D17S930-D17S1877 andD17S1857-D17S805) were mapped as candidate regions for TSGs.Conclusion Through our refined deletion mapping,we have found three candidate regions on chromosome 17 in which TSGs may be located.%目的 对胃癌17号染色体微卫星位点进行杂合缺失精细定位研究,以寻找新胃癌相关杂合缺失区域及可能存在的抑癌基因.方法 在17号染色体上筛选出13个微卫星位点,然后与48例胃癌患者的肿瘤组织及正常组织进行多重聚合酶链反应(PCR).产物在ABI Prism 3730自动荧光测序仪进行毛细管电泳,以Genemapper3.2对电泳结果以进行杂合缺失分析.使用Fisher's精确检验对杂合缺失与临床病例资料进行分析.结果 17号染色体具有较高的杂合缺失现象(31％),D17S2196、D17S808和D17S1853位点没有有效数据.其中以D17S796位点杂合缺失率最高为48％( 10/21),D17S956位点杂合缺失率最低为20％ (6/30)；结合临床病例资料发现D17S956、D17S805位点与pTNM分期相关,D17S831、D17S921位点与分化相关；通过杂合缺失研究在17号染色体上发现3个候选抑癌基因可能存在的区域D17S1857-D17S805、D17S930-D17S1877、D17S1857-D17S805.结论 通过杂合缺失精细定位分析提示17号染色体上发现3个可能存在胃癌抑癌基因的区域.