{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:26:46Z","timestamp":1768469206432,"version":"3.49.0"},"posted":{"date-parts":[[2017,1,12]]},"group-title":"Genomics","reference-count":30,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2017,1,12]],"date-time":"2017-01-12T00:00:00Z","timestamp":1484179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2017,11,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Using a dataset of somatic Structural Variants (SVs) in cancers from 2658 patients\u20141220 with corresponding gene expression data\u2014we identified hundreds of genes for which the nearby presence (within 100kb) of an SV breakpoint was associated with altered expression. For the vast majority of these genes, expression was increased rather than decreased with corresponding SV event. Well-known up-regulated cancer-associated genes impacted by this phenomenon included\n                  <jats:italic>TERT<\/jats:italic>\n                  ,\n                  <jats:italic>MDM2<\/jats:italic>\n                  ,\n                  <jats:italic>CDK4<\/jats:italic>\n                  ,\n                  <jats:italic>ERBB2<\/jats:italic>\n                  ,\n                  <jats:italic>CD274<\/jats:italic>\n                  ,\n                  <jats:italic>PDCD1LG2<\/jats:italic>\n                  , and\n                  <jats:italic>IGF2<\/jats:italic>\n                  . SVs upstream of\n                  <jats:italic>TERT<\/jats:italic>\n                  involved ~3% of cancer cases and were most frequent in liver-biliary, melanoma, sarcoma, stomach, and kidney cancers. SVs associated with up-regulation of PD1 and PDL1 genes involved ~1% of non-amplified cases. For many genes, SVs were significantly associated with either increased numbers or greater proximity of enhancer regulatory elements near the gene. DNA methylation near the gene promoter was often increased with nearby SV breakpoint, which may involve inactivation of repressor elements.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Abbreviations<\/jats:title>\n                  <jats:def-list>\n                    <jats:def-item>\n                      <jats:term>PCAWG<\/jats:term>\n                      <jats:def>\n                        <jats:p>the Pan-Cancer Analysis of Whole Genomes project<\/jats:p>\n                      <\/jats:def>\n                    <\/jats:def-item>\n                    <jats:def-item>\n                      <jats:term>SV<\/jats:term>\n                      <jats:def>\n                        <jats:p>Structural Variant<\/jats:p>\n                      <\/jats:def>\n                    <\/jats:def-item>\n                  <\/jats:def-list>\n                <\/jats:sec>","DOI":"10.1101\/099861","type":"posted-content","created":{"date-parts":[[2017,1,13]],"date-time":"2017-01-13T01:10:11Z","timestamp":1484269811000},"source":"Crossref","is-referenced-by-count":4,"title":["Whole genome and RNA sequencing of 1,220 cancers reveals hundreds of genes deregulated by rearrangement of cis-regulatory elements"],"prefix":"10.64898","author":[{"given":"Yiqun","family":"Zhang","sequence":"first","affiliation":[]},{"given":"Fengju","family":"Chen","sequence":"additional","affiliation":[]},{"given":"Nuno A.","family":"Fonseca","sequence":"additional","affiliation":[]},{"given":"Yao","family":"He","sequence":"additional","affiliation":[]},{"given":"Masashi","family":"Fujita","sequence":"additional","affiliation":[]},{"given":"Hidewaki","family":"Nakagawa","sequence":"additional","affiliation":[]},{"given":"Zemin","family":"Zhang","sequence":"additional","affiliation":[]},{"given":"Alvis","family":"Brazma","sequence":"additional","affiliation":[]},{"given":"Chad J.","family":"Creighton","sequence":"additional","affiliation":[]},{"name":"on behalf of the PCAWG Transcriptome Working Group, PCAWG Structural Variation Working Group","sequence":"additional","affiliation":[]},{"name":"ICGC\/TCGA Pan-Cancer Analysis of Whole Genomes Network","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"key":"2024080313231341000_099861v3.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1229259"},{"key":"2024080313231341000_099861v3.2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1230062"},{"key":"2024080313231341000_099861v3.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2014.07.014"},{"key":"2024080313231341000_099861v3.4","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.ajhg.2016.03.017","article-title":"Analyzing Somatic Genome Rearrangements in Human Cancers by Using Whole-Exome Sequencing","volume":"98","year":"2016","journal-title":"Am J Hum Genet"},{"key":"2024080313231341000_099861v3.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.04.010"},{"key":"2024080313231341000_099861v3.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.02.019"},{"key":"2024080313231341000_099861v3.7","doi-asserted-by":"publisher","DOI":"10.1038\/nature13379"},{"key":"2024080313231341000_099861v3.8","doi-asserted-by":"publisher","DOI":"10.1038\/nature14980"},{"key":"2024080313231341000_099861v3.9","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3722"},{"key":"2024080313231341000_099861v3.10","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad9024"},{"key":"2024080313231341000_099861v3.11","doi-asserted-by":"crossref","unstructured":"Yung, C. et al. 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