Comparing the DNA hypermethylome with gene mutations in human colorectal cancer.
Comparing the DNA hypermethylome with gene mutations in human colorectal cancer.
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DOI：
10.1371/journal.pgen.0030157
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发表时间：
2007-09
期刊：
影响因子：
4.5
通讯作者：
Baylin SB
中科院分区：
文献类型：
--
作者：
Schuebel KE;Chen W;Cope L;Glöckner SC;Suzuki H;Yi JM;Chan TA;Van Neste L;Van Criekinge W;van den Bosch S;van Engeland M;Ting AH;Jair K;Yu W;Toyota M;Imai K;Ahuja N;Herman JG;Baylin SB
我们已经开发了一种全转录组的方法来识别受启动子CpG岛DNA超甲基化和转录沉默影响的基因在结直肠癌。通过筛选细胞系并验证一组原发性人类结直肠癌样本中的肿瘤特异性超甲基化，我们估计在单个肿瘤中，所有已知基因中有近5%或更多可能是启动子甲基化的。当直接与基因突变相比时，我们发现个体肿瘤中有更多的基因高甲基化，并且个体基因中高甲基化的频率更高，这些基因包含遗传或表观遗传变化。因此，为了列举人类癌症基因组中的全部改变谱，并促进最有效的肿瘤分组以鉴定癌症生物标志物并定制治疗方法，应进行遗传和表观遗传筛选。与基因启动子CpG岛中5-甲基胞嘧啶异常积累相关的基因表达缺失是人类癌症的共同特征。在这里，我们描述了一种发现这些基因的方法，该方法允许在任何癌细胞系中鉴定数百种新的候选癌基因。我们现在估计，多达5%的结肠癌基因可能含有异常的基因高甲基化，我们将这些癌症称为“启动子CpG岛DNA高甲基化组”。最近通过癌症重测序工作鉴定的多个突变基因被证明在该超甲基化组内，并且比遗传改变更可能经历表观遗传失活。我们的方法允许衍生新的潜在肿瘤生物标志物和潜在的治疗干预途径。重要的是，我们的研究结果表明，旨在完全鉴定人类癌症基因组的努力应该包括对表观遗传和遗传变化的分析。
We have developed a transcriptome-wide approach to identify genes affected by promoter CpG island DNA hypermethylation and transcriptional silencing in colorectal cancer. By screening cell lines and validating tumor-specific hypermethylation in a panel of primary human colorectal cancer samples, we estimate that nearly 5% or more of all known genes may be promoter methylated in an individual tumor. When directly compared to gene mutations, we find larger numbers of genes hypermethylated in individual tumors, and a higher frequency of hypermethylation within individual genes harboring either genetic or epigenetic changes. Thus, to enumerate the full spectrum of alterations in the human cancer genome, and to facilitate the most efficacious grouping of tumors to identify cancer biomarkers and tailor therapeutic approaches, both genetic and epigenetic screens should be undertaken. Loss of gene expression in association with aberrant accumulation of 5-methylcytosine in gene promoter CpG islands is a common feature of human cancer. Here, we describe a method to discover these genes that permits identification of hundreds of novel candidate cancer genes in any cancer cell line. We now estimate that as much as 5% of colon cancer genes may harbor aberrant gene hypermethylation and we term these the cancer “promoter CpG island DNA hypermethylome.” Multiple mutated genes recently identified via cancer resequencing efforts are shown to be within this hypermethylome and to be more likely to undergo epigenetic inactivation than genetic alteration. Our approach allows derivation of new potential tumor biomarkers and potential pathways for therapeutic intervention. Importantly, our findings illustrate that efforts aimed at complete identification of the human cancer genome should include analyses of epigenetic, as well as genetic, changes.
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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：
3.5
作者：
Paz, MF;Wei, S;Esteller, M
通讯作者：
Esteller, M
影响因子：
30.8
作者：
Cameron, EE;Bachman, KE;Baylin, SB
通讯作者：
Baylin, SB
DOI：
10.1073/pnas.0604602103
发表时间：
2006-09-19
影响因子：
11.1
作者：
Egger, Gerda;Jeong, Shinwu;Liang, Gangning
通讯作者：
Liang, Gangning