身体结构变异对癌症蛋白质组的全球影响
Fengju Chen1, Yiqun Zhang1, Darshan S Chandrashekar2,3,4
1Dan L. Duncan Comprehensive Cancer Center Division of Biostatistics, Baylor College of Medicine, Houston, TX, USA.
Nature communications
|September 13, 2023
概括
身体结构变异 (SVs) 在癌症中影响基因表达. 这项研究将SV与瘤中的蛋白质变化联系起来,通过分析蛋白质基因组数据来确定新的治疗点.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 蛋白质组学是指蛋白质组学.
背景情况:
- 非编码体突变在癌症中至关重要.
- 整合蛋白质组和转录组数据有助于理解这些突变.
研究的目的:
- 通过使用综合蛋白质基因组数据,研究体结构变异 (SV) 断点对附近基因蛋白表达的影响.
- 识别癌症中的新型非编码变异和潜在的治疗点.
主要方法:
- 结合了基于质谱的蛋白质组学和来自1307个人类瘤的全基因组测序数据.
- 分析了 SV 断点模式及其与mRNA 和蛋白质水平的 cis 调节性改变的关联.
- 研究的SV与增强器劫持,逆转移素转位,DNA甲基化变化和融合转录有关.
主要成果:
- 大约有25%的与SV相关的mRNA变异的基因也表现出类似的蛋白质水平关联.
- 确定了特定的 SV 机制 (增强器劫持,逆转移体转移等). 导致蛋白质过度表达.
- 发现的SV和改变的蛋白质水平显著增加了体质改变关键癌症途径的患者数量.
- 编目了与患者生存相关的SV断点模式和与癌细胞依赖相关的SVs基因.
结论:
- 全癌症蛋白质基因分析揭示了通过相关放松调节的基因可向的非编码变异.
- 身体结构变异在改变蛋白质表达和影响癌症途径方面发挥着重要作用.
- 这种综合方法提高了临床相关基因组变化的识别.
相关概念视频
02:21Cancers Originate from Somatic Mutations in a Single Cell
12.0K
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...
12.0K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
7.5K
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...
7.5K
01:33Cancer-Critical Genes I: Proto-oncogenes
9.0K
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...
9.0K
01:37Epigenetic Regulation
3.1K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.1K
02:07Tumor Progression
6.4K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.4K
03:03mTOR Signaling and Cancer Progression
3.8K
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...
3.8K