{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:27:12Z","timestamp":1768476432696,"version":"3.49.0"},"posted":{"date-parts":[[2017,11,29]]},"group-title":"Cancer Biology","reference-count":84,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2017,11,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Cancer is characterised by somatic genetic variation, but the effect of the majority of non-coding somatic variants and the interface with the germline genome are still unknown. We analysed the whole genome and RNA-Seq data from 1,188 human cancer patients as provided by the Pan-cancer Analysis of Whole Genomes (PCAWG) project to map\n                  <jats:italic>cis<\/jats:italic>\n                  expression quantitative trait loci of somatic and germline variation and to uncover the causes of allele-specific expression patterns in human cancers. The availability of the first large-scale dataset with both whole genome and gene expression data enabled us to uncover the effects of the non-coding variation on cancer. In addition to confirming known regulatory effects, we identified novel associations between somatic variation and expression dysregulation, in particular in distal regulatory elements. Finally, we uncovered links between somatic mutational signatures and gene expression changes, including\n                  <jats:italic>TERT<\/jats:italic>\n                  and\n                  <jats:italic>LMO2<\/jats:italic>\n                  , and we explained the inherited risk factors in APOBEC-related mutational processes. This work represents the first large-scale assessment of the effects of both germline and somatic genetic variation on gene expression in cancer and creates a valuable resource cataloguing these effects.\n                <\/jats:p>","DOI":"10.1101\/225441","type":"posted-content","created":{"date-parts":[[2017,11,30]],"date-time":"2017-11-30T01:10:36Z","timestamp":1512004236000},"source":"Crossref","is-referenced-by-count":5,"title":["Assessing the Gene Regulatory Landscape in 1,188 Human Tumors"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8941-2620","authenticated-orcid":false,"given":"C","family":"Calabrese","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1936-298X","authenticated-orcid":false,"given":"K","family":"Lehmann","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5445-9314","authenticated-orcid":false,"given":"L","family":"Urban","sequence":"additional","affiliation":[]},{"given":"F","family":"Liu","sequence":"additional","affiliation":[]},{"given":"S","family":"Erkek","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4832-578X","authenticated-orcid":false,"given":"NA","family":"Fonseca","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3411-0692","authenticated-orcid":false,"given":"A","family":"Kahles","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6692-6154","authenticated-orcid":false,"given":"H","family":"Kilpinen","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0573-7832","authenticated-orcid":false,"given":"J","family":"Markowski","sequence":"additional","affiliation":[]},{"name":"PCAWG Group 3","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3042-9521","authenticated-orcid":false,"given":"SM","family":"Waszak","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2798-3794","authenticated-orcid":false,"given":"JO","family":"Korbel","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3789-6536","authenticated-orcid":false,"given":"Z","family":"Zhang","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5988-7409","authenticated-orcid":false,"given":"A","family":"Brazma","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5486-8532","authenticated-orcid":false,"given":"G","family":"R\u00e4tsch","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9155-4268","authenticated-orcid":false,"given":"RF","family":"Schwarz","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8818-7193","authenticated-orcid":false,"given":"O","family":"Stegle","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"key":"2019071809584429000_225441v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2657"},{"key":"2019071809584429000_225441v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12477"},{"key":"2019071809584429000_225441v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"issue":"1","key":"2019071809584429000_225441v1.4","first-page":"287","article-title":"Genome-Wide Profiling of Genetic Synthetic Lethality Identifies CDK12 as a Novel Determinant of PARP1\/2 Inhibitor Sensitivity","volume":"74","year":"2013","journal-title":"Cancer Research"},{"key":"2019071809584429000_225441v1.5","doi-asserted-by":"publisher","DOI":"10.1037\/0022-3514.51.6.1173"},{"key":"2019071809584429000_225441v1.6","doi-asserted-by":"crossref","first-page":"37393","DOI":"10.1038\/srep37393","article-title":"Changes of Bivalent Chromatin Coincide with Increased Expression of Developmental Genes in Cancer","volume":"6","year":"2016","journal-title":"Scientific Reports"},{"key":"2019071809584429000_225441v1.7","doi-asserted-by":"crossref","first-page":"44997","DOI":"10.1038\/srep44997","article-title":"Gene Expression-Based Biomarkers for Discriminating Early and Late Stage of Clear Cell Renal Cancer","volume":"7","year":"2017","journal-title":"Scientific Reports"},{"issue":"7","key":"2019071809584429000_225441v1.8","doi-asserted-by":"crossref","first-page":"e1004461","DOI":"10.1371\/journal.pgen.1004461","article-title":"Cis and Trans Effects of Human Genomic Variants on Gene Expression","volume":"10","year":"2014","journal-title":"PLoS Genetics"},{"key":"2019071809584429000_225441v1.9","doi-asserted-by":"crossref","unstructured":"Campbell, Peter J. , Gad Getz , Joshua M. 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