DNA methylation changes in atypical adenomatous hyperplasia, adenocarcinoma in situ, and lung adenocarcinoma.
DNA methylation changes in atypical adenomatous hyperplasia, adenocarcinoma in situ, and lung adenocarcinoma.
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DOI：
10.1371/journal.pone.0021443
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Laird-Offringa IA
中科院分区：
文献类型：
--
作者：
Selamat SA;Galler JS;Joshi AD;Fyfe MN;Campan M;Siegmund KD;Kerr KM;Laird-Offringa IA
异常 DNA 甲基化在肺腺癌中很常见，但其在肿瘤发展阶段的发生时间很大程度上未知。描述异常 DNA 甲基化何时出现可能有助于深入了解肺腺癌的自然史以及 DNA 甲基化改变在肿瘤形成中所起的作用。我们使用 MethyLight（一种基于实时 PCR 的灵敏定量方法）来分析 15 个 CpG 岛的 DNA 甲基化水平，这些岛在肺腺癌中经常被甲基化，并且我们已将其标记为非侵入性检测的潜在标记。我们还使用两个重复探针作为整体 DNA 低甲基化的指标。我们检查了 93 名受试者的 249 份组织样本中的 DNA 甲基化，涵盖了周围型肺腺癌发展的假定范围：组织学正常的邻近非肿瘤肺、非典型腺瘤性增生 (AAH)、原位腺癌 (AIS，以前称为细支气管肺泡癌) 和侵袭性肺 腺癌。不同病变类型之间 DNA 甲基化水平的比较表明，不同位点的 DNA 高甲基化发生在肺腺癌发展过程中的不同时间点。 CDKN2A ex2 和 PTPRN2 的 DNA 甲基化在 AAH 中已显着升高，而 2C35、EYA4、HOXA1、HOXA11、NEUROD1、NEUROD2 和 TMEFF2 的 CpG 岛在 AIS 中显着高甲基化。相比之下，CDH13、CDX2、OPCML、RASSF1、SFRP1 和 TWIST1 的高甲基化以及整体 DNA 低甲基化似乎主要存在于侵袭性癌症中。在逐渐发生更多转化的病变中，许多位点的 DNA 甲基化逐渐增加，支持了 AAH 和 AIS 是肺腺癌发展过程中连续阶段的模型。 AAH、AIS 和腺癌的 DNA 甲基化变化特征的划分开始为肿瘤发展中异常 DNA 甲基化事件制定可能的路线图。此外，它还确定了哪些 DNA 甲基化变化可用作检测浸润前病变的分子标记。
Aberrant DNA methylation is common in lung adenocarcinoma, but its timing in the phases of tumor development is largely unknown. Delineating when abnormal DNA methylation arises may provide insight into the natural history of lung adenocarcinoma and the role that DNA methylation alterations play in tumor formation. We used MethyLight, a sensitive real-time PCR-based quantitative method, to analyze DNA methylation levels at 15 CpG islands that are frequently methylated in lung adenocarcinoma and that we had flagged as potential markers for non-invasive detection. We also used two repeat probes as indicators of global DNA hypomethylation. We examined DNA methylation in 249 tissue samples from 93 subjects, spanning the putative spectrum of peripheral lung adenocarcinoma development: histologically normal adjacent non-tumor lung, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS, formerly known as bronchioloalveolar carcinoma), and invasive lung adenocarcinoma. Comparison of DNA methylation levels between the lesion types suggests that DNA hypermethylation of distinct loci occurs at different time points during the development of lung adenocarcinoma. DNA methylation at CDKN2A ex2 and PTPRN2 is already significantly elevated in AAH, while CpG islands at 2C35, EYA4, HOXA1, HOXA11, NEUROD1, NEUROD2 and TMEFF2 are significantly hypermethylated in AIS. In contrast, hypermethylation at CDH13, CDX2, OPCML, RASSF1, SFRP1 and TWIST1 and global DNA hypomethylation appear to be present predominantly in invasive cancer. The gradual increase in DNA methylation seen for numerous loci in progressively more transformed lesions supports the model in which AAH and AIS are sequential stages in the development of lung adenocarcinoma. The demarcation of DNA methylation changes characteristic for AAH, AIS and adenocarcinoma begins to lay out a possible roadmap for aberrant DNA methylation events in tumor development. In addition, it identifies which DNA methylation changes might be used as molecular markers for the detection of preinvasive lesions.
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DOI：
10.1158/1078-0432.ccr-09-0401
发表时间：
2009-07-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Baba Y;Nosho K;Shima K;Freed E;Irahara N;Philips J;Meyerhardt JA;Hornick JL;Shivdasani RA;Fuchs CS;Ogino S
通讯作者：
Ogino S
非典型腺瘤增生与原发性肺癌之间的关联。
影响因子：
8.8
作者：
Chapman AD;Kerr KM
通讯作者：
Kerr KM
影响因子：
4.8
作者：
Dai, ZY;Lakshmanan, RR;Plass, C
通讯作者：
Plass, C
影响因子：
30.8
作者：
Dammann, R;Li, C;Pfeifer, GP
通讯作者：
Pfeifer, GP
影响因子：
7.5
作者：
Dong, SM;Lee, EJ;Kim, KM
通讯作者：
Kim, KM