Proximal and distal colorectal cancers show distinct gene-specific methylation profiles and clinical and molecular characteristics
Proximal and distal colorectal cancers show distinct gene-specific methylation profiles and clinical and molecular characteristics
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DOI：
10.1016/j.ejca.2008.03.014
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发表时间：
2008-06-01
影响因子：
8.4
通讯作者：
Kim, Young S.
中科院分区：
文献类型：
--
作者：
Deng, Guoren;Kakar, Sanjay;Kim, Young S.
简介：遗传和表观遗传改变的积累导致正常结肠粘膜恶性转化为癌症。然而，近端和远端结肠癌中这些改变的频率和模式尚未得到详细检查。方法：在这项研究中，我们使用 31 个近端和 43 个远端结肠直肠癌中的 14 个标记基因检查了甲基化频率和模式。我们还分析了这些参数与临床特征、MSI、BRAF、KRAS 和 p53 突变、LOH 和整体低甲基化之间的关系。 结果：鉴定出三组具有不同程度甲基化频率的肿瘤：非常高（9%）、高（22%）和低（69%）甲基化。具有非常高和高甲基化的肿瘤表现出更频繁的近端位置、MSI、BRAF突变以及不太频繁的LOH和整体低甲基化。根据甲基化频率、MSI 状态和位置，甲基化标记可分为 3 类。近端肿瘤显示 2 型标记物、CIMP+、MSI、BRAF 突变的甲基化频率更高，LOH 和整体低甲基化频率较低，而 3 型标记物、MGMT 甲基化更频繁地与远端肿瘤、更好的生存率以及 KRAS 和 p53 基因非 CpG 位点的 G 到 A 突变相关。 结论：这些数据表明，近端和远端结直肠癌 具有独特的基因特异性甲基化谱以及分子和临床特征。 (C) 2008 Elsevier Ltd. 保留所有权利。
Introduction: Accumulation of genetic and epigenetic alterations contribute to malignant transformation of normal colonic mucosa to cancer. However, the frequency and the pattern of these alterations in proximal and distal colon cancers have not been examined in detail.Methods: In this study, we examined methylation frequencies and patterns using 14 marker genes in 31 proximal and 43 distal colorectal cancers. We also analysed the relationship between these parameters and clinical characteristics, MSI, mutations of BRAF, KRAS and p53, LOH and global hypomethylation.Results: Three groups of tumours with varying degrees of methylation frequencies were identified: very high (9%), high (22%) and low (69%) methylation. Tumours with very high and high methylation showed more frequent proximal location, MSI, BRAF mutations and less frequent LOH and global hypomethylation. The methylation markers could be classified into 3 types based on methylation frequencies, MSI status and location. Proximal tumours showed more frequent methylation of Type 2 markers, CIMP+, MSI, BRAF mutations and lower frequencies of LOH and global hypomethylation, whilst Type 3 marker, MGMT methylation was more frequently associated with distal tumours, better survival and G to A mutation in non-CpG sites in KRAS and p53 genes.Conclusion: These data showed that proximal and distal colorectal cancers have distinct gene-specific methylation profiles and molecular and clinical characteristics. (C) 2008 Elsevier Ltd. All rights reserved.