限制性标记基因组扫描分析在前列腺腺癌基因组CpG岛的异常甲基化

发布时间：2018-01-11 23:06

本文关键词：限制性标记基因组扫描分析在前列腺腺癌基因组CpG岛的异常甲基化　出处：《南方医科大学学报》2016年01期 　论文类型：期刊论文

【摘要】：目的用限制性标记基因组扫描(RLGS)分析前列腺腺癌基因组Cp G岛的异常甲基化,为前列腺腺癌相关基因的甲基化研究奠定基础。方法采用激光捕获显微切割技术从20例前列腺腺癌和18例良性前列腺增生组织中捕获均一同质的腺体细胞,提取DNA,利用RLGS技术对这些样本基因组Cp G岛扫描,比较前列腺腺癌和良性前列腺增生的Cp G岛甲基化差异,筛选出参与前列腺腺癌发生的Cp G岛甲基化基因。将其上传至DAVID数据库进行GO分析,并对筛选出甲基化最显著的基因DPYS进行焦磷酸测序。结果前列腺腺癌和良性前列腺增生分别有10245个和8658个Cp G岛发生甲基化,甲基化发生率分别为37.2%和30.3%,其中超过60%为启动子区Cp G岛。前列腺腺癌与良性前列腺增生存在差异甲基化的Cp G岛有735个,其中高甲基化458个,去甲基化256个。筛选出DPYS、P16、APC、GSTP1、TMEM122、RARB、ARHGAP20等7个前列腺腺癌甲基化最显著的基因。生物信息学分析提示这些基因涉及多个分子功能和生物过程,其中DPYS参与了13个GO注释的生物功能,50种疾病的发生发展和47个蛋白间的相互作用。对Cp G岛7个位点进行焦磷酸测序,平均甲基化频率为32.7%。可能在前列腺腺癌发生发展中存在重要的意义。结论 RLGS发现前列腺腺癌和良性前列腺增生之间存在大量Cp G岛高甲基化和去甲基化改变。筛选出甲基化显著的基因DPYS在前列腺腺癌发生和发展中起重要作用,机制有待进一步研究。
[Abstract]:Restriction labeling (RLGS) in the target genome scan analysis of prostate cancer genome Cp G island methylation and lay the foundation for the study on methylation of prostate cancer related genes. DNA extraction method using uniform homogeneous capture laser capture microdissection from 20 cases of prostate cancer and 18 cases of benign prostatic hyperplasia tissues for these samples, glandular cells, genomic Cp G island by RLGS scanning technology, Cp G island methylation difference between adenocarcinoma and benign prostatic hyperplasia of prostate, screened in Cp G island methylation based prostate cancer occurred. Due to upload it to DAVID database by GO analysis, and pyrosequencing of select the most significant methylation of DPYS gene. Results of prostate cancer and benign prostatic hyperplasia were methylated in 10245 and 8658 Cp G island methylation rates were 37.2% and 30.3%, the In more than 60% Cp in the promoter region G island. Prostate cancer and benign prostatic hyperplasia are different methylation of Cp G island has 735, including 458 high methylation, demethylation of 256 selected. DPYS, P16, APC, GSTP1, TMEM122, RARB, ARHGAP20 and other 7 prostate cancer the most significant gene methylation. Bioinformatics analysis revealed that these genes involved in multiple molecular functions and biological processes, including DPYS in 13 GO notes the biological function and interaction of the 50 kinds of diseases and 47 proteins. By pyrosequencing of Cp G island methylation average 7 loci. The frequency of 32.7%. may have important significance in the occurrence and development in prostate adenocarcinoma. Conclusion RLGS found the existence of a large number of Cp G island methylation and demethylation change between prostate cancer and benign prostatic hyperplasia were selected. DPYS gene was methylated in prostatic adenocarcinoma It plays an important role in the development and development, and the mechanism needs to be further studied.

【作者单位】：广东省人民医院//广东省医学科学院泌尿外科;广东省人民医院//广东省医学科学院生殖医学科;
【基金】：广东省科技计划(2011B031800092)
【分类号】：R737.25
【正文快照】： 限制性标记基因组扫描(restriction landmarkgenomic scanning,RLGS)是一种有效的基因扫描技术,能鉴别DNA的放大效应和异常的DNA甲基化[1-2]。前列腺癌新发病例已超越肺癌成为男性恶性肿瘤发病的第一位[3]。目前国内外依然使用前列腺特异性抗原(PSA)和直肠指检对前列腺癌进

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