线粒体DNA中的D环突变是食道癌中化疗耐药性的危险因素
Takashi Harino1, Koji Tanaka2, Daisuke Motooka3
1Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2-E2, Yamada-Oka, Suita, Osaka, 565-0871, Japan.
Scientific reports
|December 31, 2024
概括
化疗可以诱导食道癌中线粒体DNA (mtDNA) 的突变. 在mtDNA的HVS1区域的特定突变与化疗耐药性和较差的生存结果有关.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 生物化学 生化学
背景情况:
- 食道癌是侵略性的,耐化疗是治疗的主要挑战.
- 线粒体DNA (mtDNA) 比核DNA更容易发生突变,并影响细胞功能.
- 在食道癌中,化疗诱导的mtDNA突变尚未得到充分理解.
研究的目的:
- 在食道癌中识别化疗诱导的mtDNA突变.
- 将这些突变与临床病理因素和化疗耐药性相关联.
- 研究mtDNA突变在治疗结果中的作用.
主要方法:
- 下一代测序用于分析食道状细胞癌 (ESCC) 细胞系和患者样本中的mtDNA.
- 样本包括化疗前后的细胞系和患者组织.
- 分析的重点是识别mtDNA突变及其与临床数据的关联.
主要成果:
- 化疗治疗导致mtDNA突变的增加,特别是在D环区域.
- 在D循环的超变段1 (HVS1) 内的突变与mtDNA复制数的减少有关.
- HVS1突变与化学疗法反应较差以及五年生存率下降相关.
结论:
- 在化疗后获得的mtDNA中的HVS1突变可能会导致食道癌的治疗耐药性.
- 这些发现突出了化学疗法耐药性和不良预后的潜在机制.
- 了解这些mtDNA变异可以为克服食道癌治疗挑战的策略提供信息.
相关概念视频
Treatment Resistant Cancers
3.2K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.2K
Electron Transport Chain: Complex I and II
11.3K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
11.3K
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


