突变不匹配修复基因和微卫星不稳定状态在胰腺癌中的突变
Marina Emelyanova1, Anna Ikonnikova1, Alexander Pushkov2
1Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
Cancers
|June 19, 2024
概括
微卫星不稳定性 (MSI) 在胰腺癌 (PC) 中很少见,即使有不匹配修复 (MMR) 基因突变. 这项研究没有发现MSI高的瘤,强调需要在免疫治疗前评估Lynch综合征的PC患者的MMR缺乏.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 癌症研究 癌症研究
背景情况:
- 胰腺癌 (PC) 患有不匹配修复 (MMR) 缺陷的患者可能会对免疫疗法产生反应.
- 微卫星不稳定性 (MSI) 是MMR缺陷 (MMR-D) 的一个关键指标.
研究的目的:
- 为了确定PC中MSI的流行率.
- 调查MMR基因 (MLH1,MSH2,MSH6) 中的生殖系和体质突变.
- 评估MMR基因突变与PC中的MSI状态之间的联系.
主要方法:
- 来自PC患者的临床样本的下一代定向测序 (正常/瘤配对,仅瘤,仅正常).
- 在235个PC病例中使用PCR进行MSI状态评估.
- 在MMR基因中识别和分析生殖系和体质变异.
主要成果:
- 在MMR基因中发现的致病性/可能致病性生殖系变异在1.1%的患者中;体变异在2.6%中.
- 在研究队列中没有检测到微卫星不稳定性高 (MSI-H) 的瘤.
- 在PC中MSI不常见,即使在瘤中也存在MMR基因突变.
结论:
- 在胰腺癌中MSI是罕见的.
- 评估瘤MMR-D状态对于考虑免疫治疗的林奇综合征PC患者至关重要.
相关概念视频
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
Cancers Originate from Somatic Mutations in a Single Cell
11.9K
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...
11.9K
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
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
Mutagenicity and Carcinogenicity
1.2K
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...
1.2K


