Genome-wide DNA methylation profiling of non-small cell lung carcinomas.
Genome-wide DNA methylation profiling of non-small cell lung carcinomas.
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DOI：
10.1186/1756-8935-5-9
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发表时间：
2012-06-22
影响因子：
3.9
通讯作者：
Philipsen S
中科院分区：
文献类型：
--
作者：
Carvalho RH;Haberle V;Hou J;van Gent T;Thongjuea S;van Ijcken W;Kockx C;Brouwer R;Rijkers E;Sieuwerts A;Foekens J;van Vroonhoven M;Aerts J;Grosveld F;Lenhard B;Philipsen S
非小细胞肺癌(NSCLC)是一种复杂的恶性肿瘤，由于其异质性和预后差，给诊断、预后和患者治疗带来了许多挑战。DNA甲基化是表观遗传调控的重要机制，参与正常发育和癌症的发生。它是一种非常稳定和特异的修饰，因此原则上是一种非常适合肿瘤表观遗传表型的标记。在这里，我们提出了非小细胞肺癌样本和配对肺组织的全基因组DNA甲基化分析，其中我们结合了甲基帽和下一代测序(甲基帽-序列)，以提供肿瘤和配对肺样本的全面DNA甲基化图谱。通过亚硫酸氢盐测序和所选区域的甲基特异性聚合酶链式反应验证了甲基帽-SEQ数据。对甲基苯丙氨酸序列数据的分析表明，重复实验之间以及成对的肿瘤/肺样本之间存在很强的正相关性。我们确定了57个存在于所有非小细胞肺癌肿瘤中的差异甲基化区域(DMR)。虽然低甲基化的DMRS与任何特定功能类别的基因都没有关联，但高甲基化的DMR与编码转录调节因子的基因密切相关。此外，在非小细胞肺癌样本中，亚端粒区和卫星重复序列发生了低甲基化。我们还鉴定了两种主要的非小细胞肺癌亚型--腺癌和鳞状细胞癌的DMR。总的来说，我们提供了一个资源，包含了非小细胞肺癌及其配对肺组织的全基因组DNA甲基化图谱，以及非小细胞肺癌中已知和新的DMR及其相关基因的全面列表。
Non-small cell lung carcinoma (NSCLC) is a complex malignancy that owing to its heterogeneity and poor prognosis poses many challenges to diagnosis, prognosis and patient treatment. DNA methylation is an important mechanism of epigenetic regulation involved in normal development and cancer. It is a very stable and specific modification and therefore in principle a very suitable marker for epigenetic phenotyping of tumors. Here we present a genome-wide DNA methylation analysis of NSCLC samples and paired lung tissues, where we combine MethylCap and next generation sequencing (MethylCap-seq) to provide comprehensive DNA methylation maps of the tumor and paired lung samples. The MethylCap-seq data were validated by bisulfite sequencing and methyl-specific polymerase chain reaction of selected regions. Analysis of the MethylCap-seq data revealed a strong positive correlation between replicate experiments and between paired tumor/lung samples. We identified 57 differentially methylated regions (DMRs) present in all NSCLC tumors analyzed by MethylCap-seq. While hypomethylated DMRs did not correlate to any particular functional category of genes, the hypermethylated DMRs were strongly associated with genes encoding transcriptional regulators. Furthermore, subtelomeric regions and satellite repeats were hypomethylated in the NSCLC samples. We also identified DMRs that were specific to two of the major subtypes of NSCLC, adenocarcinomas and squamous cell carcinomas. Collectively, we provide a resource containing genome-wide DNA methylation maps of NSCLC and their paired lung tissues, and comprehensive lists of known and novel DMRs and associated genes in NSCLC.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
30.8
作者：
Dammann, R;Li, C;Pfeifer, GP
通讯作者：
Pfeifer, GP
影响因子：
8
作者：
Helman, E.;Naxerova, K.;Kohane, I. S.
通讯作者：
Kohane, I. S.