原发性胃癌染色体7q31的最小共同缺失区域及其意义  

Minimal Commonly Deleted Regions on Chromosome 7q31 in Primary Gastric Carcinoma and Its Clinical Significance

作　　者：李锦添[1,2] 付莉[1,2] 夏建川[1,2] 冯炳健[1,2] 买世娟[1,2] 余杏娟[1,2] 黄丽惜[1,2] 冯启胜[1,2] 潘志忠[1,3] 詹友庆[1,3] 

机构地区：[1]华南肿瘤学国家重点实验室 [2]中山大学肿瘤防治中心实验研究部,广东广州510060 [3]中山大学肿瘤防治中心腹科,广东广州510060

出　　处：《癌症》2005年第11期1306-1311,共6页Chinese Journal of Cancer

基　　金：国家自然科学基金(No.30070840)~~

摘　　要：背景与目的:先前的研究显示7号染色体长臂(7q)在原发性胃癌有高频缺失;位于7q31的D7S486是7q上最高频的杂合性缺失(lossofheterozygosity,LOH)位点,且该位点的LOH频率与肿瘤的淋巴结转移显著相关;推测D7S486位点附近可能存在胃癌相关的抑癌基因(tumorsuppressorgene,TSG)。为能在更小的区域内找寻胃癌相关的TSGs,本研究通过检测原发性胃癌在7q31区域内微卫星标记位点的LOH情况,确定胃癌的最小共同缺失区域,并分析它们在胃癌发病中的可能作用。方法:以D7S486位点为中心,在位于其上下的7q31区域内选取平均遗传距离约0.5厘摩(centimorgan,cM)的12个微卫星标记。显微切割78例原发性胃癌和相应的正常胃粘膜组织,分别提取DNA;进行多重PCR扩增,聚丙烯酰胺凝胶电泳分离PCR产物,以GeneScan、Genotyper软件分析各微卫星位点的LOH情况。根据LOH结果作图,确定胃癌在7q31内的最小共同缺失区域,并与临床病理指标联系,分析区域缺失在胃癌发病中的可能作用。结果:12个微卫星标记位点均可在原发性胃癌中出现LOH,总的LOH频率为41.7%(40/72)。LOH的最高频位点是D7S486(位于7q31.2),为30.4.%(17/56);次高频位点是D7S650(位于7q31.3),为21.1%(8/38)。原发性胃癌在7q31内有两个最小共同缺失区域,分别为D7S2543～D7S486和D7S480～D7S650(长度均约为90kb)。D7S2543～D7S486区域缺失的频率与胃癌患者的临床分期和淋巴结转移显著相关(P=0.01和P=0.03);D7S480～D7S650区域缺失的频率与胃癌患者的临床分期显著相关(P=0.03),且该区域缺失仅出现于临床Ⅲ/Ⅳ期、T3/T4期或淋巴结转移的患者。结论:原发性胃癌在染色体7q31上存在两个最小共同缺失区域,分别为D7S2543～D7S486和D7S480～D7S650;在这两个区域内可能存在胃癌发展密切相关的抑癌基因。BACKGROUND ＆ OBJECTIVE： Previous studies have showed that chromosome 7q occurs a high frequency of loss of heterozygosity （LOH） in primary gastric carcinoma; D7S486 located in 7q31 is a locus with the highest frequency of LOH on 7q, which is significantly related to lymph node metastasis of tumor, Gastric carcinoma-related tumor suppressor genes （TSGs） might locate near the locus. In order to seek gastric carcinoma-related TSGs in a further narrow region, LOH of microsatellite marker loci on chromosome 7q31 was examined in primary gastric carcinoma to determine the minimal commonly deleted regions, and the possible roles of these regional deletions in gastric carcinoma pathogenesis were analyzed in this study. METHODS： Twelve microsatellite markers centering D7S486 locus on 7q31 region, with an average genetic distance of about 0.5 centimorgan （cM）, were selected. DNAs were extracted from 78 specimens of gastric carcinoma and corresponding normal gastric mucosa tissues, amplified through multipolymerase chain reaction （multi- PCR）, and separated by electrophoresis. LOH of microsatellite marker loci was analyzed with GeneScan and Genotyper software to determine the minimal commonly deleted regions on 7q31. The possible roles of these regional deletions in gastric carcinoma pathogenesis were analyzed with consideration of clinicopathologic parameters. RESULTS： LOH of all 12 selected microsatellite marker loci was detected in primary gastric carcinoma, with the total frequency of 41.7% （40/72）. The most frequent LOH was D7S486 locus （located in 7q31.2）, with the frequency of 30.4% （17/56）; the second was D7S650 locus （located in 7q31.3）, with the frequency of 21.1% （8/38）. Two minimal commonly deleted regions, D7S2543-D7S486 and D7S480-D7S650 （each span about 90 kb）, were detected on 7q31 in primary gastric carcinoma. The LOH frequency of D7S2543-D7S486 region was significantly related to clinical stage and lymph node metastasis（P=0.01, P=0.03）; the LOH frequency o

关 键 词：胃肿瘤 染色体7q31 杂合性缺失 

分 类 号：R735.2[医药卫生—肿瘤]