한빛사 논문
Yuan Yuan1,15, Young Seok Ju2,3,15, Youngwook Kim4,15, Jun Li1, Yumeng Wang5,1, Christopher J. Yoon3, Yang Yang6, Inigo Martincorena2, Chad J. Creighton7, John N. Weinstein1,8, Yanxun Xu9, Leng Han10, Hyung-Lae Kim11, Hidewaki Nakagawa12, Keunchil Park13,†, Peter J. Campbell2,14,†, Han Liang1,8,5,† and PCAWG Consortium*
1Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 2Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK. 3Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea. 4Department of Health Science and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea. 5Quantitative and Computational Biosciences Graduate Program, Baylor College of Medicine, Houston, TX, USA. 6Division of Biostatistics, The University of Texas Health Science Center at Houston School of Public Health, Houston, TX, USA. 7Department of Medicine and Dan L. Duncan Cancer Center Division of Biostatistics, Baylor College of Medicine, Houston, TX, USA. 8Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 9Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, USA. 10Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX, USA. 11Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, Korea. 12Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. 13Division of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 14Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. 15These authors contributed equally: Yuan Yuan, Young Seok Ju, Youngwook Kim. *A list of members and affiliations appears in the Supplementary Note
†To whom correspondence should be addressed.
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.
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