Age-related hypermethylation of the 5' region of MLH1 in normal colonic mucosa is associated with microsatellite-unstable colorectal cancer development.
Age-related hypermethylation of the 5' region of MLH1 in normal colonic mucosa is associated with microsatellite-unstable colorectal cancer development.
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发表时间：
2001-10
期刊：
影响因子：
11.2
通讯作者：
H. Nakagawa;G. Nuovo;E. Zervos;E. Martin;R. Salovaara;L. Aaltonen;A. Chapelle
中科院分区：
文献类型：
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作者：
H. Nakagawa;G. Nuovo;E. Zervos;E. Martin;R. Salovaara;L. Aaltonen;A. Chapelle
MLH1启动子的高甲基化是大多数具有微卫星不稳定性（MSI）的散发性结直肠癌的基础。为了研究高甲基化在正常结肠黏膜中作为一种可能的前驱病变的作用，我们对MLH1上游700bp涵盖51个CpG位点进行了研究。我们在34名80岁及以上患者中的15名（44%）发现了部分甲基化的等位基因（P = 0.0026）。在33名患有MSI +肿瘤的患者中有18名（55%）存在完全甲基化的等位基因，但在90名患有MSI -肿瘤的患者中仅有18名（20%）存在（P = 0.00019）。通过原位分析，甲基化呈斑片状，主要位于靠近管腔的隐窝区域。我们得出结论，正常结肠黏膜中MLH1启动子甲基化的扩散与年龄以及散发性MSI +结直肠癌的发生密切相关。
Hypermethylation of the MLH1 promoter underlies most sporadic colorectal cancers with microsatellite instability (MSI). To investigate the role of hypermethylation in the normal colonic mucosa as a possible precursor lesion, we studied 700 bp upstream of MLH1 covering 51 CpG sites. We found partially methylated alleles in 15 of 34 (44%) patients or =80 years of age (P = 0.0026). Fully methylated alleles were present in 18 of 33 (55%) patients with MSI+ tumors but in only 18 of 90 (20%) patients with MSI- tumors (P = 0.00019). By in situ analysis, methylation was patchy and located mainly in the cryptal regions close to the lumen. We conclude that the spread of methylation in the MLH1 promoter in the normal colonic mucosa is closely associated with age and the development of sporadic MSI+ colorectal cancers.