@article{4e2bb0a32e764f3da0ff7a8f24d544cb,
title = "Analyzing Somatic Genome Rearrangements in Human Cancers by Using Whole-Exome Sequencing",
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.",
author = "Lixing Yang and Lee, {Mi Sook} and Hengyu Lu and Oh, {Doo Yi} and Kim, {Yeon Jeong} and Donghyun Park and Gahee Park and Xiaojia Ren and Bristow, {Christopher A.} and Haseley, {Psalm S.} and Soohyun Lee and Angeliki Pantazi and Raju Kucherlapati and Park, {Woong Yang} and Scott, {Kenneth L.} and Choi, {Yoon La} and Park, {Peter J.}",
note = "Funding Information: The results published here are in whole or in part based upon data generated by The Cancer Genome Atlas (TCGA) project established by the National Cancer Institute and the National Human Genome Research Institute. Information about the TCGA and the investigators and institutions who constitute the TCGA research network can be found at http://cancergenome.nih.gov . This work was supported by the Harvard Ludwig Center (P.J.P.), NIH grant U24CA144025 (R.K. and P.J.P.), National Research Foundation grants NRF-2013M3C8A1078501, NRF-2013R1A2A2A01068922 (Y.L.C.) and 2015R1C1A1A02037066 (M.L.) funded by the Korean Ministry of Science, Information and Communications Technology & Future Planning, Cancer Prevention and Research Institute of Texas grants RP140102 (H.L.) and RP120046 (K.L.S), and NIH grant U01CA168394 (K.L.S). This work made use of the Bionimbus Protected Data Cloud. Publisher Copyright: {\textcopyright} 2016 The American Society of Human Genetics.",
year = "2016",
month = may,
day = "5",
doi = "10.1016/j.ajhg.2016.03.017",
language = "English (US)",
volume = "98",
pages = "843--856",
journal = "American journal of human genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "5",
}