乳腺癌中的复发性和功能调节突变
Esther Rheinbay1,2, Prasanna Parasuraman2, Jonna Grimsby1
1The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02124, USA.
Nature
|June 29, 2017
概括
致癌突变通常发生在促进器区域,而不仅仅是编码基因. 这项研究确定了乳腺癌的关键促进突变,影响了基因表达,揭示了癌症研究的新途径.
科学领域:
- 基因组学
- 癌症生物学
- 分子瘤学
背景情况:
- 基因组分析主要集中在癌症基因识别的编码区域.
- 非编码区域,特别是促进体,对于它们在癌症发育中的作用缺乏研究.
研究的目的:
- 通过深度测序来确定乳腺癌中显著突变的促进子区域.
- 研究这些促进子突变对基因表达的功能后果.
主要方法:
- 在360个原发性乳腺癌样本中进行深度测序.
- 开发用于检测显著突变的促进体的计算方法.
- 对转录因子结合和基因表达的突变影响分析.
主要成果:
- 在三个基因:FOXA1,RMRP和NEAT1的促进体中发现了复发性突变.
- 在激素受体阳性乳腺癌中,FOXA1促进体突变通过E2F结合的增加导致过度表达.
- 在RMRP和NEAT1促进者的突变改变蛋白质结合和基因表达水平.
结论:
- 发起区域具有与编码区域相似的频率,在癌症中具有重复性,功能意义的突变.
- 这些发现强调了非编码区域在癌症基因组学中的重要性.
- 需要对大量患者进行进一步的深度测序,以发现更多与癌症相关的促进子突变.
相关概念视频
Cancers Originate from Somatic Mutations in a Single Cell
15.1K
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...
15.1K
Loss of Tumor Suppressor Gene Functions
6.2K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
6.2K
The Retinoblastoma Gene
4.8K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.8K
Cancer-Critical Genes II: Tumor Suppressor Genes
9.9K
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...
9.9K
Cancer-Critical Genes I: Proto-oncogenes
11.6K
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...
11.6K
mTOR Signaling and Cancer Progression
4.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
4.9K


