Identification of a panel of sensitive and specific DNA methylation markers for squamous cell lung cancer.

Identification of a panel of sensitive and specific DNA methylation markers for squamous cell lung cancer.
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DOI:
10.1186/1476-4598-7-62
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发表时间:
2008-07-10
期刊:
影响因子:
37.3
通讯作者:
Laird-Offringa IA
Laird-Offringa IA
中科院分区:
医学1区
文献类型:
--
作者:
Anglim PP;Galler JS;Koss MN;Hagen JA;Turla S;Campan M;Weisenberger DJ;Laird PW;Siegmund KD;Laird-Offringa IA

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在美国和西欧,肺癌是男性和女性癌症死亡的主要原因。每年有超过16万美国人死于这种疾病。五年生存率为15%--明显低于其他主要癌症。早期发现是提高肺癌患者生存率的关键因素。DNA高甲基化被认为是肿瘤抑制基因失活的重要机制,可为肺癌的早期检测提供强有力的生物标志物。在这里,我们专注于开发肺鳞状细胞癌的DNA甲基化标记。利用灵敏、高通量的DNA甲基化分析技术,我们检测了来自同一患者的45例鳞状细胞肺癌样本和邻近非肿瘤肺组织中42个基因座的甲基化情况。我们在肿瘤组织中发现了22个DNA甲基化水平显著高于邻近非肿瘤肺组织的基因座。在这些基因中,有8个在肿瘤组织中表现出高度显著的甲基化(p<0.0001):GDNF、MTHFR、OPCML、TNFRSF25、TCF21、PAX8、PTPRN2和PITX2。在我们的标本收集中结合使用,这个八位点组显示出95.6%的敏感性和特异性。我们已经确定了22个鳞状细胞肺癌的DNA甲基化标志物,其中几个以前没有报道过在任何类型的人类癌症中甲基化。排名前八位的标志物显示出作为鳞状细胞肺癌敏感和特异的DNA甲基化标志物小组的巨大前景。
Lung cancer is the leading cause of cancer death in men and women in the United States and Western Europe. Over 160,000 Americans die of this disease every year. The five-year survival rate is 15% – significantly lower than that of other major cancers. Early detection is a key factor in increasing lung cancer patient survival. DNA hypermethylation is recognized as an important mechanism for tumor suppressor gene inactivation in cancer and could yield powerful biomarkers for early detection of lung cancer. Here we focused on developing DNA methylation markers for squamous cell carcinoma of the lung. Using the sensitive, high-throughput DNA methylation analysis technique MethyLight, we examined the methylation profile of 42 loci in a collection of 45 squamous cell lung cancer samples and adjacent non-tumor lung tissues from the same patients. We identified 22 loci showing significantly higher DNA methylation levels in tumor tissue than adjacent non-tumor lung. Of these, eight showed highly significant hypermethylation in tumor tissue (p < 0.0001): GDNF, MTHFR, OPCML, TNFRSF25, TCF21, PAX8, PTPRN2 and PITX2. Used in combination on our specimen collection, this eight-locus panel showed 95.6% sensitivity and specificity. We have identified 22 DNA methylation markers for squamous cell lung cancer, several of which have not previously been reported to be methylated in any type of human cancer. The top eight markers show great promise as a sensitive and specific DNA methylation marker panel for squamous cell lung cancer.
DOI: 10.1038/sj.neo.7900162
发表时间: 2001-07-01
期刊: NEOPLASIA
影响因子: 4.8
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