Deep Sequencing Revealed a CpG Methylation Pattern Associated With ALDH1L1 Suppression in Breast Cancer.
Deep Sequencing Revealed a CpG Methylation Pattern Associated With ALDH1L1 Suppression in Breast Cancer.
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DOI：
10.3389/fgene.2018.00169
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发表时间：
2018
影响因子：
3.7
通讯作者：
Dmitriev AA
中科院分区：
文献类型：
--
作者：
Beniaminov AD;Puzanov GA;Krasnov GS;Kaluzhny DN;Kazubskaya TP;Braga EA;Kudryavtseva AV;Melnikova NV;Dmitriev AA
启动子CpG岛的高甲基化是公认的癌症基因沉默的表观遗传机制。然而，关于这种表观遗传标记如何触发基因下调过程的分子细节仍然难以捉摸。在这里，我们使用深度亚硫酸盐测序和qPCR分析来研究16对不同临床分期的乳腺癌（BC）样本中ALDH1L1启动子区域CpG甲基化的模式及其与基因表达水平的关系。在所有检测的BC样本中，ALDH1L1基因的表达被抑制高达200倍，启动子区域的平均高甲基化水平与ALDH1L1下调呈正相关。我们通过相关分析确定了ALDH1L1启动子内每个CpG位点在异常基因表达中的作用，包括上游非转录区、第一个非翻译外显子和第一个内含子的起始位置。研究发现甲基化对基因转录强度影响最大的CpG位点。大多数CpG位点位于ALDH1L1基因的第一个内含子的紧凑区域。这些结果有助于揭示CpG启动子超甲基化的动态性质，并证明深度亚硫酸盐测序在寻找癌症中新的表观遗传标记方面的效率。
Hypermethylation of promoter CpG islands is generally recognized epigenetic mechanism responsible for gene silencing in cancer. However, molecular details on how this epigenetic mark triggers the process of gene downregulation are still elusive. Here, we used deep bisulfite sequencing and qPCR analysis to investigate the pattern of CpG methylation of ALDH1L1 promoter region and its association with the gene expression level in 16 paired breast cancer (BC) samples of different clinical stages. Expression of ALDH1L1 gene was suppressed in all examined BC samples up to 200-fold, and average hypermethylation level of the promoter region correlated positively with ALDH1L1 downregulation. We determined the role of every individual CpG site within the ALDH1L1 promoter, including upstream untranscribed region, first untranslated exon, and the start of the first intron, in aberrant gene expression by correlation analysis. The search revealed CpG sites which methylation has the highest impact on intensity of gene transcription. The majority of such CpG sites are located in a compact region in the first intron of the ALDH1L1 gene. These results assist in unraveling of dynamic nature of CpG promoter hypermethylation as well as demonstrate the efficiency of deep bisulfite sequencing in search for novel epigenetic markers in cancer.
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影响因子：
5.1
作者：
Krupenko, Sergey A.
通讯作者：
Krupenko, Sergey A.
DOI：
10.1007/978-1-4939-6685-1_15
发表时间：
2017-01-01
期刊：
ORAL BIOLOGY: MOLECULAR TECHNIQUES AND APPLICATIONS, 2ND EDITION
影响因子：
--
作者：
Chatterjee, Aniruddha;Rodger, Euan J.;Stockwell, Peter A.
通讯作者：
Stockwell, Peter A.
影响因子：
64.5
作者：
Ciriello G;Gatza ML;Beck AH;Wilkerson MD;Rhie SK;Pastore A;Zhang H;McLellan M;Yau C;Kandoth C;Bowlby R;Shen H;Hayat S;Fieldhouse R;Lester SC;Tse GM;Factor RE;Collins LC;Allison KH;Chen YY;Jensen K;Johnson NB;Oesterreich S;Mills GB;Cherniack AD;Robertson G;Benz C;Sander C;Laird PW;Hoadley KA;King TA;TCGA Research Network;Perou CM
通讯作者：
Perou CM
影响因子：
5.6
作者：
Melnikova NV;Dmitriev AA;Belenikin MS;Koroban NV;Speranskaya AS;Krinitsina AA;Krasnov GS;Lakunina VA;Snezhkina AV;Sadritdinova AF;Kishlyan NV;Rozhmina TA;Klimina KM;Amosova AV;Zelenin AV;Muravenko OV;Bolsheva NL;Kudryavtseva AV
通讯作者：
Kudryavtseva AV
影响因子：
--
作者：
Dmitriev AA;Rudenko EE;Kudryavtseva AV;Krasnov GS;Gordiyuk VV;Melnikova NV;Stakhovsky EO;Kononenko OA;Pavlova LS;Kondratieva TT;Alekseev BY;Braga EA;Senchenko VN;Kashuba VI
通讯作者：
Kashuba VI