在流行遗传部位出现体质突变的发病率较高
Mengyao Wang1,2, Shuai Cheng Li1, Bairong Shen3,4
1Department of Computer Science, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong, China.
Briefings in bioinformatics
|March 1, 2024
概括
代表常见的人类基因组部位的常见位点,比非常见位点更快地积累体质突变 (csmVariants). 这些csmVariants与更好的癌症患者存活率有关,特别是在不匹配修复缺陷的情况下.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 人类遗传学 人类遗传学
背景情况:
- 常见基因位点是人类基因组的位置,其中至少有1%的人口存在遗传变异.
- 身体突变发生在常见的和非常见的位置,假定类似的概率.
- 了解常见位点的突变模式对于癌症研究至关重要.
研究的目的:
- 为了研究突变率和体质突变的特征在常见的局部与非常见的局部相比.
- 探索癌症患者常见的体质变异 (csmVariants) 的临床意义.
- 确定影响癌症发生过程中csmVariants积累的因素.
主要方法:
- 来自癌症基因组图谱 (TCGA) 的体质突变数据的分析.
- 突变发生率,复发率和常见和非常见局部之间的突变背景的比较.
- csm变异率,患者存活率和诸如不匹配修复缺陷之类的分子特征之间的相关性分析.
主要成果:
- 共同的位点,占所有位点的1.03%,占TCGA体质突变的5.14%.
- 在常见位置的体质突变发生率是非常见位置的2.7倍.
- 与ncsmVariants相比,csmVariants的复发率 (2.59x),C-to-T转换在CpG位点 (2.93x),与衰老相关的突变特征 (5.5x) 和帕林德罗姆语境 (1.84x) 显著更高.
- 更高的csmVariant率与更好的无进展生存率相关,特别是在不匹配修复缺陷的患者中.
结论:
- 常见的位置是人体基因组内体质突变的热点, csm 变种表现出明显的特征.
- 诸如帕林德罗姆序列,衰老和DNA不匹配修复缺陷等因素影响了csm变体积累.
- 增加的csmVariants与改善的患者结果有关,这表明潜在的治疗影响.
相关概念视频
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
Cancer Prevention
6.2K
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...
6.2K
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
Mutations
37.3K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
37.3K
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
Cancer-Critical Genes I: Proto-oncogenes
8.9K
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...
8.9K


