在结直肠和子宫内膜癌基因组中微卫星不稳定的景观
Tae-Min Kim1, Peter W Laird, Peter J Park
1Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA; Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
Cell
|November 12, 2013
概括
由DNA修复缺陷引起的微卫星不稳定性 (MSI) 在结直肠和子宫内膜癌中显示出瘤特异性模式. 这种基因组不稳定性会影响基因表达,并受到染色体组织的影响.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 分子遗传学 分子遗传学
背景情况:
- 微卫星,或简单的双重重复,在人类基因组中是丰富的.
- 在DNA不匹配修复中的缺陷可以导致微卫星缩短或延长,这种现象被称为微卫星不稳定性 (MSI).
- MSI是某些癌症的已知标志,但需要全面的全基因组理解.
研究的目的:
- 在癌症中进行微卫星不稳定性 (MSI) 的全基因组分析.
- 调查MSI的患病率,突变谱和功能后果.
- 探索MSI,瘤类型和染色体组织之间的关系.
主要方法:
- 来自277个结直肠和子宫内膜癌基因组的外体和全基因组测序数据的分析.
- 微卫星不稳定事件的识别和描述.
- 对MSI分布与跨基因组区域的点突变进行比较分析.
主要成果:
- 在编码序列中确定了具有瘤类型特异性的复发性MSI事件.
- 与野生类型等位基因相比,观察到MSI事件的高移到内比率和较低的转录水平.
- 发现MSI的显著基因组分布,在euchromatic和intronic区域的过度代表和核细胞所占位置的枯竭.
结论:
- 癌症基因组中的MSI表现出显著的瘤类型特异性.
- MSI影响基因表达,并受到区域染色体组织的影响.
- 这项研究提供了MSI在癌症基因组学中的作用的全面观点.
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