AIM: To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients.METHODS: Seven fluorescent...AIM: To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients.METHODS: Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by χ2 test.RESULTS: Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (< 30%) by detailed deletion mapping. Significant opposite difference was observed between LOH frequency and tumor diameter on D4S412 and D4S1546 locus (0% vs 16.67%, P = 0.041; 54.55% vs 11.11%, P = 0.034, respectively). On D4S403 locus, LOH was significantly associated with tumor gross pattern (11.11%, 0, 33.33%, P = 0.030). No relationship was detected on other loci compared with clinicopathologial features.CONCLUSION: By deletion mapping, two obvious high frequency LOH regions spanning D4S3013 (4p15.2) and D4S405 (4p14) locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm).展开更多
目的确定有家族史鼻咽癌患者4p15．1-4q12区域等位基因杂合性丢失（loss of heterozygosity，LOH）的分布和频率，为进一步缩小该区域内易感基因的范围提供新的线索和依据。方法收集具有家族史的鼻咽癌患者石蜡包埋的活检组织标本，采...目的确定有家族史鼻咽癌患者4p15．1-4q12区域等位基因杂合性丢失（loss of heterozygosity，LOH）的分布和频率，为进一步缩小该区域内易感基因的范围提供新的线索和依据。方法收集具有家族史的鼻咽癌患者石蜡包埋的活检组织标本，采用显微切割的方法在肿瘤组织石蜡切片上分离肿瘤细胞和正常淋巴细胞，选定7个定位于4p15．1-4q12区域内的高密度微卫星位点，多重PCR扩增和丙烯酰胺凝胶电泳后，Genescan软件对各位点LOH进行分析。结果25例具家族史鼻咽癌患者中，23例在4p15．1-4q12区至少存在一个微卫星位点的LOH（92％）。其中D4S2382位点LOH的频率最高，达到56％；D4S350和D4S1547位点LOH频率均约为50％。最小共同缺失区位于位点D4S350和D4S1547之间。结论鼻咽癌4p15．1—4q12区域内的易感基因可能位于微卫星位点D4S350和D4S1547附近。展开更多
基金Supported by The National Natural Science Foundation of China, No. 30080016 and No. 30470977
文摘AIM: To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients.METHODS: Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by χ2 test.RESULTS: Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (< 30%) by detailed deletion mapping. Significant opposite difference was observed between LOH frequency and tumor diameter on D4S412 and D4S1546 locus (0% vs 16.67%, P = 0.041; 54.55% vs 11.11%, P = 0.034, respectively). On D4S403 locus, LOH was significantly associated with tumor gross pattern (11.11%, 0, 33.33%, P = 0.030). No relationship was detected on other loci compared with clinicopathologial features.CONCLUSION: By deletion mapping, two obvious high frequency LOH regions spanning D4S3013 (4p15.2) and D4S405 (4p14) locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm).
文摘目的确定有家族史鼻咽癌患者4p15．1-4q12区域等位基因杂合性丢失（loss of heterozygosity，LOH）的分布和频率，为进一步缩小该区域内易感基因的范围提供新的线索和依据。方法收集具有家族史的鼻咽癌患者石蜡包埋的活检组织标本，采用显微切割的方法在肿瘤组织石蜡切片上分离肿瘤细胞和正常淋巴细胞，选定7个定位于4p15．1-4q12区域内的高密度微卫星位点，多重PCR扩增和丙烯酰胺凝胶电泳后，Genescan软件对各位点LOH进行分析。结果25例具家族史鼻咽癌患者中，23例在4p15．1-4q12区至少存在一个微卫星位点的LOH（92％）。其中D4S2382位点LOH的频率最高，达到56％；D4S350和D4S1547位点LOH频率均约为50％。最小共同缺失区位于位点D4S350和D4S1547之间。结论鼻咽癌4p15．1—4q12区域内的易感基因可能位于微卫星位点D4S350和D4S1547附近。
