从人类癌症基因组中获得的体质突变的全面目录
Erin D Pleasance1, R Keira Cheetham, Philip J Stephens
1Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
Nature
|December 18, 2009
概括
这项研究对个体恶性黑色素瘤的体质突变进行了分类,揭示了紫外线作为主要的突变特征. 它强调了转录区域的优先DNA修复,为癌症基因组进化提供了洞察力.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 分子瘤学分子瘤学
背景情况:
- 癌症的特征是体质突变,驱动突变影响发育,乘客突变是中性的.
- 了解个体癌症的突变格局对于破译癌症基因组进化至关重要.
研究的目的:
- 创建个人恶性黑色素瘤体质突变的第一个全面目录.
- 调查塑造癌症基因组的潜在力量,包括DNA损伤,修复和选择过程.
主要方法:
- 恶性黑色素瘤的全基因组测序和来自同一个人的匹配的淋巴细胞细胞系.
- 分析突变特征和整个基因组的分布模式.
主要成果:
- 确定紫外线暴露是主要的突变特征,与已知的黑色素瘤风险因素一致.
- 观察到突变分布不均,基因足迹的流行率较低,这表明转录区域的DNA修复优先.
- 综合突变目录揭示了DNA损伤,修复和选择在临床症状出现前几年的运作痕迹.
结论:
- 癌症基因组测序为DNA损伤,修复和选择的历史过程提供了强大的洞察力.
- 这些发现强调了环境因素,如紫外线辐射在塑造癌症基因组中的重要作用.
- 偏好的DNA修复机制有助于癌症基因组内的突变分布不均.
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When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
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