癌症突变的蛋白质结构背景揭示了分子机制和候选驱动基因
Diego Chillón-Pino1, Mihaly Badonyi1, Colin A Semple1
1MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Cell reports
|October 23, 2024
概括
这项研究使用蛋白质结构分析了数百万种癌症突变. 瘤抑制基因表现出破坏性突变,而瘤基因具有较轻的,集群突变,有助于驱动基因识别.
科学领域:
- 基因组学就是基因组学.
- 结构生物学 结构生物学
- 癌症研究 癌症研究
背景情况:
- 蛋白质结构的确定和建模使人类遗传变异的大规模分析成为可能.
- 了解突变的结构背景对于癌症研究至关重要.
研究的目的:
- 基于结构位置和预测效应,分析数以百万计的癌症相关误解突变.
- 为了识别区分瘤抑制剂和瘤基因的独特模式.
- 开发用于识别候选癌症驱动基因的方法.
主要方法:
- 对数百万癌症相关误解突变的分析.
- 评估突变结构位置和预测的扰乱效应.
- 评估集体蛋白质突变特性和三维聚类.
主要成果:
- 瘤抑制剂富含结构性破坏性突变 (功能丧失).
- 瘤基因突变通常在结构上是温和的,有利于功能获取.
- 三维突变聚类对瘤基因具有很高的预测性,将其与非癌症基因区分开来.
结论:
- 独特的结构突变模式区分了瘤抑制剂和瘤基因.
- 结构分析,特别是突变聚类,有助于识别癌症驱动基因.
- 这些发现对分析癌症测序数据和理解分子作用具有实用性.
相关概念视频
Cancers Originate from Somatic Mutations in a Single Cell
11.8K
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...
11.8K
Cancer-Critical Genes I: Proto-oncogenes
8.7K
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...
8.7K
Cancer-Critical Genes II: Tumor Suppressor Genes
7.3K
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...
7.3K
Adaptive Mechanisms in Cancer Cells
5.7K
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,...
5.7K
Cancer Prevention
6.1K
Several factors can increase the risk of cancer in an individual. About 50% of cancer cases can be prevented by adopting a healthy lifestyle, regular exercise, eating healthy, and following a modest cancer prevention diet. Epidemiological studies have consistently shown that populations with vegetable and fruit-rich diets have reduced the incidence of cancer. On the other hand, populations who have a diet rich in animal fat, red meat, junk food, or high calories are predisposed to cancer.
Some...
Some...
6.1K
mTOR Signaling and Cancer Progression
3.7K
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...
3.7K


