贲门癌中染色体8p21-p23杂合性丢失的研究

染色体Sp21-p23区域存在与多种肿瘤相关的抑癌基因。为明确该染色体区域的抑癌基因与贲门癌的关系，我们进行了贲门癌中染色体8p21-p23区域微卫星标记的杂合性丢失研究。首先采用激光捕获显微切割技术从19例贲门癌组织中获得均质的肿瘤细胞及正常的胃粘膜细胞，然后利用多重置换扩增技术扩增捕获细胞的全基因组DNA。选择覆盖染色体8p21-p23区域的13个微卫星标记，利用PCR结合硝酸银染色方法分析了肿瘤细胞中染色体8p21-p23的杂合性丢失情况。结果显示，在贲门癌中染色体8p21-p23的总丢失频率高达63．2％（12／19），单一标记的丢失频率为25％～55．6％。根据不同肿瘤组织中杂合性丢失的情况，我们确定了一个最小缺失区域，即8p22GGAA-8p22ATCT标记间约1．2Mb的范围。研究结果表明，染色体8p22区域抑癌基因在贲门癌发生发展中起重要作用；染色体最小重叠区域的确定对最终鉴定该区域内的抑癌基因有参考价值。

肺癌染色体8p21～23区域精细缺失图谱的构建

目的：进一步明确肺癌在 8p21～ 23区域等位基因杂合性丢失（ loss of heterozygosity, LOH）的频率与共同缺失区范围，以便分离该区域内与肺癌相关的候选抑瘤基因。方法：应用位于 8p21～ 23的 16个微卫星多态标记，对 32例肺癌组织和 2例肺癌细胞系进行 LOH分析。结果： 32例肺癌组织与 2例肺癌细胞系中共 20例（ 58.82％）存在至少一个位点的杂合性丢失，缺失频率最高的位点是 8p21.1的 NEFL与 D8s1771及 8p21.3的 D8s133，其频率分别为 45.16％（ 14/31）、 37.03％（ 11/27）和 35.72％（ 10/28）。 7例患者在 D8s1771～ D8s1477间存在连续性共同缺失。结论：肺癌在 8p21～ 23的最小共同缺失区位于 8p21的 D8s1771～ D8s1477之间，该区域可能存在一个与肺癌发生发展密切相关的抑瘤基因。

Cloning, tissue expression pattern characterization and chromosome localization of human peptide methionine sulfoxide reductase cDNA

Oxidation and reduction of some amino acids are one of the molecular mechanisms for regulating the function of proteins. The oxidation of methionine (Met) to methionine sulfoxide (Met(O)) results in decreasing or loss of the biological activity of related proteins. It was found that peptide methionine sulfoxide reductase (msrA) can reduce Met(O) to Met and therefore restored the biological function of the oxidized proteins. To reveal the methionine oxidation-reduction mechanism in human body, in this study, the cDNA sequence of bovine msrA was used as an information-probe to screen the human EST database. Based on a contig assembled from homologous ESTs, a 1 256-bp human MSRA cDNA was cloned from several human cDNA libraries. The cDNA contains an open reading frame (ORF) of 705 bp in length, which encodes 235 amino acid residues. Homology comparison revealed that human MSRA shares 88% and 61% identities with bovine and Escherichia coli msrA protein respectively. Expression pattern analysis revealed a