한빛사 논문
Abstract
Lixing Yang1,11, Mi-Sook Lee2,11, Hengyu Lu3,11, Doo-Yi Oh2, Yeon Jeong Kim4,5, Donghyun Park4,5, Gahee Park4, Xiaojia Ren6, Christopher A. Bristow7, Psalm S. Haseley1,6, Soohyun Lee1, Angeliki Pantazi8, Raju Kucherlapati6,8, Woong-Yang Park2,4, Kenneth L. Scott3,12, Yoon-La Choi2,9,12,*, Peter J. Park1, 6, 10, 12,*
1 Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
2 Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul 06351, Korea
3 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
4 Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea
5 Samsung Biomedical Research Institute, Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co., Seoul 06351, Korea
6 Division of Genetics, Brigham and Women’s Hospital, Boston, MA 02115, USA
7 Department of Genomic Medicine and Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
8 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
9 Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
10 Ludwig Center, Harvard Medical School, Boston, MA 02115, USA
11 These authors contributed equally to this work
12 These authors contributed equally to this work
*correspondence : Yoon-La Choi, Peter J. Park
Abstract
Although exome sequencing data are generated primarily to detect single-nucleotide variants and indels, they can also be used to identify a subset of genomic rearrangements whose breakpoints are located in or near exons. Using >4,600 tumor and normal pairs across 15 cancer types, we identified over 9,000 high confidence somatic rearrangements, including a large number of gene fusions. We find that the 5' fusion partners of functional fusions are often housekeeping genes, whereas the 3' fusion partners are enriched in tyrosine kinases. We establish the oncogenic potential of ROR1-DNAJC6 and CEP85L-ROS1 fusions by showing that they can promote cell proliferation in vitro and tumor formation in vivo. Furthermore, we found that ∼4% of the samples have massively rearranged chromosomes, many of which are associated with upregulation of oncogenes such as ERBB2 and TERT. Although the sensitivity of detecting structural alterations from exomes is considerably lower than that from whole genomes, this approach will be fruitful for the multitude of exomes that have been and will be generated, both in cancer and in other diseases.
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