大规模重复进化的理论和癌症驱动核酸 (CDN) 的完整识别
Lingjie Zhang1, Tong Deng1, Zhongqi Liufu1,2
1State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
eLife
|December 17, 2024
概括
识别致癌核酸 (CDN) 对于理解瘤发生至关重要. 这项研究提出了一种方法,通过分析大型癌症基因组数据集中的突变复发模式来识别几乎所有CDN.
科学领域:
- 基因组学和计算生物学
- 癌症研究 癌症研究
- 进化医学是一种进化医学.
背景情况:
- 瘤发生的结果是累积的突变,癌症驱动核酸 (CDN) 是关键驱动因素.
- 目前对CDN的识别是有限的,瘤中的大多数突变都是非驱动因素.
- 了解CDN的全部组件对于个性化癌症治疗至关重要.
研究的目的:
- 根据突变复发情况,开发一种理论框架来识别致癌核酸 (CDN).
- 通过使用中立进化原则,建立一个区分CDN与乘客突变的门.
- 评估全面CDN识别的可行性,并增加样本大小.
主要方法:
- 在TCGA癌症数据库 (n=300-1000) 中分析点突变复发模式.
- 探索突变特征以确定在中性进化条件下的复发极限 (i).
- 理论建模以确定所需的样本大小 (n=100,000) 以实现近乎完整的CDN识别.
主要成果:
- 在i≥3重复发生的突变被确定为CDN,因为中性进化不能解释这种频率.
- 目前的方法已经确定了不到10%的CDN.
- 预计将样本规模增加到每种癌症类型的10万个,从而能够识别几乎所有CDN.
结论:
- 提出的理论提供了一种强大的方法来识别致癌核酸 (CDN).
- 全面的CDN识别将阐明瘤发生机制,并增强基因向疗法.
- 准确识别CDN有望提供更有效和耐药的癌症治疗方法.
更多相关视频
08:46Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
10.5K
08:23Single Droplet Digital Polymerase Chain Reaction for Comprehensive and Simultaneous Detection of Mutations in Hotspot Regions
Published on: September 25, 2018
13.1K
相关概念视频
02:21Cancers Originate from Somatic Mutations in a Single Cell
11.5K
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...
11.5K
02:53Adaptive Mechanisms in Cancer Cells
5.7K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.7K
02:07Tumor Progression
6.2K
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...
6.2K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
7.3K
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...
7.3K
01:38Nucleotide Excision Repair
3.4K
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...
3.4K
01:33Cancer-Critical Genes I: Proto-oncogenes
8.7K
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...
8.7K