Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in lung cancer.
Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in lung cancer.
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DOI：
10.1186/1479-5876-8-86
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发表时间：
2010-09-17
影响因子：
7.4
通讯作者：
Sánchez-Carbayo M
中科院分区：
文献类型：
--
作者：
Castro M;Grau L;Puerta P;Gimenez L;Venditti J;Quadrelli S;Sánchez-Carbayo M
包括抑癌基因在内的关键癌症基因的DNA甲基化变化可以发生在癌症发生的早期，这可能是癌症的重要早期指标。这项研究的目的是检验一种多重方法来评估肿瘤抑制基因甲基化作为肺癌的肿瘤分层和临床结果预后生物标志物。一个多条件的探针小组使用甲基化特异的多重连接依赖的探针放大分析(MS-MLPA)询问了肺癌中18个抑癌基因的DNA异常甲基化状态。应用MS-MLPA对7例肺癌细胞株和54例原发肺肿瘤细胞株进行检测。肺癌细胞系中频繁甲基化的基因包括SCGB3A1、ID4、CCND2在所分析的肺癌中发现最常见的甲基化基因。HLTF、BNIP3、H2AFX、CACNA1G、TGIF、ID4和CACNA1A被鉴定为肺癌中甲基化的新候选抑癌基因。肺癌中最常见的甲基化基因是SCGB3A1和DLC1(均为50.0%)。鳞癌和腺癌中ID4、DCL1、BNIP3、H2AFX、CACNA1G和TIMP3基因甲基化的发生率有显著差异。当比较局部肿瘤和转移肿瘤时，RUNX3、SCGB3A1、sFRP4和DLC1的甲基化与疾病的程度显著相关。此外，HTLF、SFRP5和TIMP3基因甲基化与总生存率显著相关。MS-MLPA可用于某些类型的肺肿瘤的分类和临床预后预测。后者为肺癌患者的临床治疗提供了一种辅助策略，具有临床意义。
Changes in DNA methylation of crucial cancer genes including tumor suppressors can occur early in carcinogenesis, being potentially important early indicators of cancer. The objective of this study was to examine a multiplexed approach to assess the methylation of tumor suppressor genes as tumor stratification and clinical outcome prognostic biomarkers for lung cancer. A multicandidate probe panel interrogated DNA for aberrant methylation status in 18 tumor suppressor genes in lung cancer using a methylation-specific multiplex ligation-dependent probe amplification assay (MS-MLPA). Lung cancer cell lines (n = 7), and primary lung tumors (n = 54) were examined using MS-MLPA. Genes frequently methylated in lung cancer cell lines including SCGB3A1, ID4, CCND2 were found among the most commonly methylated in the lung tumors analyzed. HLTF, BNIP3, H2AFX, CACNA1G, TGIF, ID4 and CACNA1A were identified as novel tumor suppressor candidates methylated in lung tumors. The most frequently methylated genes in lung tumors were SCGB3A1 and DLC1 (both 50.0%). Methylation rates for ID4, DCL1, BNIP3, H2AFX, CACNA1G and TIMP3 were significantly different between squamous and adenocarcinomas. Methylation of RUNX3, SCGB3A1, SFRP4, and DLC1 was significantly associated with the extent of the disease when comparing localized versus metastatic tumors. Moreover, methylation of HTLF, SFRP5 and TIMP3 were significantly associated with overall survival. MS-MLPA can be used for classification of certain types of lung tumors and clinical outcome prediction. This latter is clinically relevant by offering an adjunct strategy for the clinical management of lung cancer patients.
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影响因子：
2.4
作者：
Buyru, Nur;Altinisik, Julide;Dalay, Nejat
通讯作者：
Dalay, Nejat
影响因子：
254.7
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Jeuken, Judith W. M.
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5.7
作者：
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通讯作者：
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影响因子：
11.5
作者：
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通讯作者：
Wu, Xifeng