在癌症基因组中突变和选择的签名
Graham R Bignell1, Chris D Greenman, Helen Davies
1Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Nature
|February 19, 2010
概括
研究人员在癌症细胞系中发现了成千上万的同卵性缺失,揭示了癌症基因组进化的洞察力. 这些发现有助于区分DNA破裂和癌症发展中的选择压力.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 分子遗传学 分子遗传学
背景情况:
- 癌症基因组是由体突变和选择所塑造的.
- 癌症中的同卵性缺失可以向衰退的癌症基因或脆弱的部位.
- 癌症中的许多同卵性缺失仍然无法解释.
研究的目的:
- 在一大群癌症细胞系中识别和表征体质同卵性缺失.
- 开发方法来区分 homozygous 删除的原因.
- 了解突变和选择在塑造癌症基因组中的作用.
主要方法:
- 在746个癌细胞系中分析了2,428个体质同卵性缺失.
- 导出结构特征以区分删除原因.
- 将签名应用于无法解释的删除集群.
主要成果:
- 发现同卵性缺失影响了11%的蛋白质编码基因,表明它们对细胞存活不至关重要.
- 结构签名成功地区分了脆弱部位的删除与衰退性癌症基因的删除.
- 大多数不明原因的缺失发生在脆弱的区域,其中较小的部分涉及衰退性癌症基因.
结论:
- 结构签名是剖析癌症基因组突变与选择影响的宝贵工具.
- 癌症细胞系为癌症生物学和药物发现研究提供了丰富的数据.
- 了解同卵性缺失有助于破译癌症基因组进化和识别潜在的治疗点.
相关概念视频
Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
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.
Such genes that act...
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.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
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.
Such genes that act...
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.
Such genes that act...
Adaptive Mechanisms in Cancer Cells
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Cancer
Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.


