Manders Freek, van Dinter Jip, van Boxtel Ruben
Princess Máxima Center for Pediatric Oncology and Oncode Institute, Heidelberglaan 25, 3584CS Utrecht, The Netherlands.
iScience. 2022 Nov 16;25(12):105610. doi: 10.1016/j.isci.2022.105610. eCollection 2022 Dec 22.
Mitochondria are small organelles that play an essential role in the energy production of eukaryotic cells. Defects in their genomes are associated with diseases, such as aging and cancer. Here, we analyzed the mitochondrial genomes of 532 whole-genome sequencing samples from cancers and normal clonally expanded single cells. We show that the mitochondria of normal cells accumulate mutations with age and that most of the mitochondrial mutations found in cancer are the result of healthy mutation accumulation. We also show that the normal HSPCs of patients with leukemia have an increased mitochondrial mutation load. Finally, we show that secondary pediatric cancers and chemotherapy treatments do not impact the mitochondrial mutation load and mtDNA copy numbers of most cells, suggesting that damage to the mitochondrial genome is not a major driver for carcinogenesis. Overall, these findings may contribute to our understanding of mitochondrial genomes and their role in cancer.
线粒体是在真核细胞能量产生中起关键作用的小细胞器。其基因组缺陷与衰老和癌症等疾病相关。在此，我们分析了来自癌症和正常克隆扩增单细胞的532个全基因组测序样本的线粒体基因组。我们发现正常细胞的线粒体随年龄增长积累突变，且癌症中发现的大多数线粒体突变是健康突变积累的结果。我们还表明白血病患者的正常造血干细胞线粒体突变负荷增加。最后，我们发现继发性儿童癌症和化疗治疗不会影响大多数细胞的线粒体突变负荷和线粒体DNA拷贝数，这表明线粒体基因组损伤不是致癌的主要驱动因素。总体而言，这些发现可能有助于我们理解线粒体基因组及其在癌症中的作用。
