前列腺癌基因外显子区突变位点筛查及与前列腺癌易感性的关系

发布时间：2018-04-26 19:38

  本文选题：前列腺肿瘤 + 前列腺癌　； 参考：《山东医药》2017年19期

【摘要】：目的筛查前列腺癌(PCA)基因外显子区的突变位点,并分析其与PCA易感性的关系。方法 6例PCA患者,留取PCA组织和癌旁正常组织标本。采用液相杂交捕获技术分析PCA、癌旁正常组织全基因外显子区的单核苷酸多态性(SNPs),采用Illumina Hi Seq 2000平台高通量测序将捕获富集并验证的PCA、癌旁正常组织基因外显子区SNPs的DNA文库进行突变位点比对,筛选PCA基因外显子区突变位点。采用bwa软件与参考基因组hg19作比对,分析PCA外显子区功能性突变位点的生物信息学信息,分析功能性突变位点与PCA易感性的关系。结果共发现4个未报道的功能性SNPs突变位点,分别为BRCA1 rs16941、MET rs45483396、P53 rs121912655、COPB2 rs7374710。进一步通过临床样本检测结果显示,BRCA1 rs16941与COPB2 rs7374710两个SNP不仅均与PCA易感性相关(OR分别为1.47,1.27;95%CI分别为1.14~1.72;1.20~1.41),而且与PCA患者PSA值及Gleason评分均呈正相关(OR分别为1.25,1.37;95%CI=1.10~1.84,1.20~2.34;P均0.01)。结论 PCA外显子区存在BRCA1 rs16941、COPB2 rs7374710功能性突变位点,携带有BRCA1 rs16941、COPB2 rs7374710突变位点的个体罹患PCA的可能性较高。
[Abstract]:Objective to screen the mutation sites in the exon of prostate cancer (PCA) gene and to analyze the relationship between the mutation and the susceptibility to PCA. Methods the specimens of PCA and adjacent normal tissues were collected from 6 patients with PCA. The single nucleotide polymorphisms (SNPs) in the whole exon region of the normal tissues adjacent to the cancer were analyzed by liquid phase hybridization technique. High throughput sequencing on the Illumina Hi Seq 2000 platform was used to detect the gene exon region of the precancerous normal tissue. The DNA library of SNPs was compared with the mutation locus. The mutation site of exon region of PCA gene was screened. The bioinformatics information of functional mutation site in exon of PCA was analyzed by bwa software and reference genomic hg19, and the relationship between functional mutation site and susceptibility of PCA was analyzed. Results A total of 4 unreported functional SNPs mutations were found, namely BRCA1 rs16941, met rs45483396, p53 rs121912655, COPB2 rs7374710. Furthermore, the results of clinical sample test showed that the OR of BRCA1 rs16941 and COPB2 rs7374710 were not only 1.47 / 1.2795 CI = 1.14 / 1.72 / 1.201.41 / 1, respectively, but also 1.251.3795CI1.101.81.41.20 / 2.34C / r = 1.251.3795CI1.101.81.41.20 / 2.34 / 1 respectively (P = 0.01). Conclusion there is a functional mutation site of BRCA1 rs16941 (COPB2) rs7374710 in the exon of PCA, and individuals with BRCA1 rs16941 (COPB2) rs7374710 mutation are more likely to develop PCA.
【作者单位】： 南通大学第三附属医院暨无锡市第三人民医院;
【基金】：无锡市医院管理中心医学科研联合攻关项目(YGZXL1203;YGZXL 1318) 无锡市科技发展资金(CSE31N1605)
【分类号】：R737.25
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本文编号：1807419