美国纪念斯隆-凯特琳癌症中心Ed Reznik等研究人员合作发现，核基因组与线粒体基因组的共调控驱动肿瘤中单细胞mtDNA的动态变化。相关论文于2024年5月13日在线发表在《自然—遗传学》杂志上。

据介绍，肿瘤mtDNA拷贝数和基因型的细胞间变异程度，以及这种变异的表型和进化后果，还没有得到很好的描述。

附：英文原文

Title: Single-cell mtDNA dynamics in tumors is driven by coregulation of nuclear and mitochondrial genomes

Author: Kim, Minsoo, Gorelick, Alexander N., Vzquez-Garca, Ignacio, Williams, Marc J., Salehi, Sohrab, Shi, Hongyu, Weiner, Adam C., Ceglia, Nick, Funnell, Tyler, Park, Tricia, Boscenco, Sonia, OFlanagan, Ciara H., Jiang, Hui, Grewal, Diljot, Tang, Cerise, Rusk, Nicole, Gammage, Payam A., McPherson, Andrew, Aparicio, Sam, Shah, Sohrab P., Reznik, Ed

Issue&Volume: 2024-05-13

Abstract: The extent of cell-to-cell variation in tumor mitochondrial DNA (mtDNA) copy number and genotype, and the phenotypic and evolutionary consequences of such variation, are poorly characterized. Here we use amplification-free single-cell whole-genome sequencing (Direct Library Prep (DLP+)) to simultaneously assay mtDNA copy number and nuclear DNA (nuDNA) in 72,275 single cells derived from immortalized cell lines, patient-derived xenografts and primary human tumors. Cells typically contained thousands of mtDNA copies, but variation in mtDNA copy number was extensive and strongly associated with cell size. Pervasive whole-genome doubling events in nuDNA associated with stoichiometrically balanced adaptations in mtDNA copy number, implying that mtDNA-to-nuDNA ratio, rather than mtDNA copy number itself, mediated downstream phenotypes. Finally, multimodal analysis of DLP+ and single-cell RNA sequencing identified both somatic loss-of-function and germline noncoding variants in mtDNA linked to heteroplasmy-dependent changes in mtDNA copy number and mitochondrial transcription, revealing phenotypic adaptations to disrupted nuclear/mitochondrial balance.

DOI: 10.1038/s41588-024-01724-8

Source: https://www.nature.com/articles/s41588-024-01724-8