科学家揭示人肿瘤中线粒体基因组的特征
2020-02-11   阅读:425   来源:自然

美国德克萨斯大学MD安德森癌症中心Han Liang、英国惠康桑格研究所Peter J. Campbell和韩国成均馆大学医学院Keunchil Park合作揭示了人类癌症中线粒体基因组的分子特点。这一研究成果在线发表在2020年2月5日的《自然—遗传学》上。

作为国际肿瘤基因组协会/全基因组联盟全基因组泛癌分析的一部分,该联合会汇总了38种肿瘤类型中2658例癌症样本的全基因组测序数据,研究人员对线粒体基因组和相关的RNA测序数据进行了多维综合分析。研究人员的揭示了最明确的线粒体基因组突变图谱,并确定了一些超突变病例。截断突变在肾癌、结直肠癌和甲状腺癌中显著富集,这提示信号通路的激活具有致癌作用。研究人员发现线粒体DNA存在频繁的体细胞核转移,其中一些破坏了治疗靶基因。线粒体拷贝数在癌细胞内和细胞间差异很大,并且与临床变量相关。基因共表达分析显示线粒体基因在氧化磷酸化、DNA修复和细胞周期中的功能,并揭示了它们与临床上可操作基因间的联系。该研究为将线粒体生物学转化为临床应用奠定了基础。

据了解,线粒体是必不可少的细胞器,在癌症中也起关键作用。

附:英文原文

Title: Comprehensive molecular characterization of mitochondrial genomes in human cancers

Author: Yuan Yuan, Young Seok Ju, Youngwook Kim, Jun Li, Yumeng Wang, Christopher J. Yoon, Yang Yang, Inigo Martincorena, Chad J. Creighton, John N. Weinstein, Yanxun Xu, Leng Han, Hyung-Lae Kim, Hidewaki Nakagawa, Keunchil Park, Peter J. Campbell, Han Liang

Issue&Volume: 2020-02-05

Abstract: Mitochondria are essential cellular organelles that play critical roles in cancer. Here, as part of the International Cancer Genome Consortium/The Cancer Genome Atlas Pan-Cancer Analysis of Whole Genomes Consortium, which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we performed a multidimensional, integrated characterization of mitochondrial genomes and related RNA sequencing data. Our analysis presents the most definitive mutational landscape of mitochondrial genomes and identifies several hypermutated cases. Truncating mutations are markedly enriched in kidney, colorectal and thyroid cancers, suggesting oncogenic effects with the activation of signaling pathways. We find frequent somatic nuclear transfers of mitochondrial DNA, some of which disrupt therapeutic target genes. Mitochondrial copy number varies greatly within and across cancers and correlates with clinical variables. Co-expression analysis highlights the function of mitochondrial genes in oxidative phosphorylation, DNA repair and the cell cycle, and shows their connections with clinically actionable genes. Our study lays a foundation for translating mitochondrial biology into clinical applications.

DOI: 10.1038/s41588-019-0557-x

编辑:小柯机器人

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