基本的免疫瘤性权衡定义了驱动器突变适应性
David Hoyos1, Roberta Zappasodi2,3,4,5, Isabell Schulze6,7
1Computational Oncology, Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature
|May 11, 2022
概括
癌症驱动突变聚集在热点中. 一个新的
科学领域:
- 癌症学
- 癌症基因组学
- 进化生物学
背景情况:
- 癌症中的误解驱动突变对特定热点具有显著的突变倾向.
- 现有的模型没有全面整合导致这种现象的各种因素.
- 了解癌症的进化驱动因素对于开发有效疗法至关重要.
研究的目的:
- 提出一个统一的理论框架,整合多式数据以建模癌症驱动突变.
- 调查TP53热点突变的致癌潜力和免疫性之间的进化权衡.
- 根据突变特征预测患者的结果和瘤发病情况.
主要方法:
- 开发一个"自由适应性"生物物理模型,整合基因组,表观遗传,转录组和蛋白质组数据.
- 推断突变的p53度和分析TP53热点突变.
- 使用癌症基因组图谱,免疫治疗患者数据和健康个体数据集验证模型预测.
主要成果:
- TP53热点突变代表了最佳的进化解决方案,平衡了致癌优势和免疫逃避.
- 这种模型准确地预测了患者的存活时间,免疫疗法的反应,以及瘤发病的年龄.
- 热点突变的差异免疫性经过实验验证实.
结论:
- "自由适应"框架为了解癌症驱动突变的演变提供了统一的方法.
- 免疫选择性压力在癌症和非癌症病变中起着不同的作用.
- 这些发现对精确免疫疗法和早期癌症干预策略有影响.
更多相关视频
12:04Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells
Published on: March 10, 2023
3.8K
09:37Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
1.9K
相关概念视频
Mismatch Repair
5.3K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
5.3K
Cancer-Critical Genes I: Proto-oncogenes
9.2K
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...
9.2K
Mutagenicity and Carcinogenicity
1.4K
Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
1.4K
Cancer-Critical Genes II: Tumor Suppressor Genes
8.2K
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...
8.2K
Loss of Tumor Suppressor Gene Functions
5.1K
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...
5.1K
Mouse Models of Cancer Study
5.7K
Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
5.7K
