在黑色素瘤中,DNA甲基化对DNA损伤反应的变化与生存率和局部免疫状态有关
Min Wang1, Xiao-Dong Zhang1, Han-Qing Yang1
1Department of Burns and Plastic Surgery, Changzhou Wujin People's Hospital, Changzhou, China.
Immunity, inflammation and disease
|September 10, 2024
概括
DNA甲基化变化显著影响黑色素瘤的预后和免疫反应. 一个新的4-CpG签名预测了黑色素瘤患者的生存和免疫治疗结果.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 免疫学 免疫学 免疫学
背景情况:
- 黑色素瘤的预后和治疗反应受复杂的分子因素的影响.
- 了解DNA损伤反应 (DDR) 和表观遗传修饰之间的相互作用对于推进黑色素瘤治疗至关重要.
研究的目的:
- 研究DNA甲基化改变对黑色素瘤中DNA损伤反应 (DDR) 的影响.
- 为了将这些变化与黑色素瘤预后,免疫微环境和对免疫治疗的反应相关联.
主要方法:
- 用集成的分子和临床数据分析各种黑色素瘤队列.
- 在与DDR相关的CpG位点上应用层次聚类来识别黑色素瘤亚型.
- 开发和验证4-CpG风险评分签名,用于生存和免疫治疗预测.
主要成果:
- 通过独特的DDR配置文件,预后和免疫反应特征的独特黑色素瘤亚型被确定.
- 这些亚型虽然表现出类似的瘤突变负担,但对免疫治疗的反应不同.
- 一个验证的4-CpG签名有效地预测了患者的存活率和免疫疗法的有效性.
结论:
- 在DNA甲基化,DDR,瘤免疫力和黑色素瘤患者的结果之间存在显著的相互关系.
- 表观遗传修饰,特别是DNA甲基化模式,是黑色素瘤对治疗反应的关键决定因素.
- 开发的4-CpG签名为个性化黑色素瘤治疗策略提供了一个有前途的工具.
相关概念视频
Epigenetic Regulation
3.0K
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...
3.0K
Nucleotide Excision Repair
3.5K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.5K
Overview of DNA Repair
30.9K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
30.9K
DNA Damage can Stall the Cell Cycle
9.1K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.1K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Mismatch Repair
4.8K
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...
4.8K


