动态和持续的De Novo L1逆转换有助于卵巢癌中的基因组可塑性和内科异质性
Barun Pradhan1, Jaana Oikkonen1, Kaiyang Zhang1
1University of Helsinki, Helsinki, Finland.
Cancer research
|November 12, 2025
概括
在卵巢癌中,LINE-1 (L1) 逆转移素是活跃的,导致瘤异质. 高的L1活性与增殖相关,而低的活动表明免疫反应. L1插入提供了潜在的精准医学目标.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 分子瘤学分子瘤学
背景情况:
- 在人类基因组中,LINE-1 (L1) 逆转移素是活跃的,特别是在癌症中.
- L1逆转换有助于基因组不稳定性和瘤进化.
- L1活性与患者内瘤异质性有关.
研究的目的:
- 在高度血清性卵巢癌 (HGSC) 中量化 de novo L1 插入.
- 调查L1插入负担和瘤特征之间的关系.
- 在个别患者中探索L1插入配置文件.
主要方法:
- 在HGSC临床样本中对de novo L1插入的量化.
- 分析L1插入负担及其与增殖和免疫通路的相关性.
- 在患者中比较L1插入配置文件和单核酸变异 (SNV) 配置文件.
主要成果:
- 在HGSC患者之间观察到L1插入事件 (L1负担) 的显著异质性.
- 高L1负担的瘤呈现出高增殖率;低L1负担的瘤显示出免疫反应和细胞死亡途径的丰富.
- 在不同瘤部位的同一患者内,L1插入配置文件的差异明显大于SNV配置文件.
结论:
- 在体内,L1活性和逆转换是动态的,这有助于瘤基因组的可塑性.
- 患者特定的L1负担可能会受到原始瘤分子特性的影响.
- 与L1逆转换相关的DNA损伤对精密癌症医学具有潜在的脆弱性.
相关概念视频
Non-LTR Retrotransposons
13.1K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
13.1K
Overview of Transposition and Recombination
18.7K
Transposons make up a significant part of genomes of various organisms. Therefore, it is believed that transposition played a major evolutionary role in speciation by changing genome sizes and modifying gene expression patterns. For example, in bacteria, transposition can lead to conferring antibiotic resistance. Movement of transposable elements within the genetic pool of pathogenic bacteria can aid in transfer of antibiotic-resistant genetic elements. In eukaryotes, transposons can carry out...
18.7K
LTR Retrotransposons
19.4K
LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
19.4K
Cancers Originate from Somatic Mutations in a Single Cell
14.5K
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...
14.5K
piRNA - Piwi-interacting RNAs
7.5K
PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
7.5K
Conservative Site-specific Recombination and Phase Variation
6.6K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.6K


