{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:47:44Z","timestamp":1788173264591,"version":"build-2803163510"},"posted":{"date-parts":[[2024,12,17]]},"group-title":"Genomics","reference-count":74,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T00:00:00Z","timestamp":1734393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>LINE-1 (L1) retrotransposition is widespread in many cancers, especially those with a high burden of chromosomal rearrangements. However, whether and to what degree L1 activity directly impacts genome integrity is unclear. Here, we apply whole-genome sequencing to experimental models of L1 expression to comprehensively define the spectrum of genomic changes caused by L1. Combining the analyses of experimental models of L1 induction and of cancer genomes, we demonstrate that L1 retrotransposition can directly generate reciprocal translocations, genomic DNA inversions, and foldback rearrangements resulting from illegitimate recombination of double-strand DNA ends generated by L1-encoded ORF2p. We further show that L1-induced rearrangements can produce unstable chromosomes that fuel the acquisition of complex rearrangements, large segmental copy-number alterations, and genetic heterogeneity through breakage-fusion bridge cycles or DNA fragmentation. Together, these findings suggest L1 as a potent mutagenic force capable of driving genome evolution in cancers.<\/jats:p>","DOI":"10.1101\/2024.12.14.628481","type":"posted-content","created":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T03:41:17Z","timestamp":1734752477000},"source":"Crossref","is-referenced-by-count":19,"title":["Chromosomal rearrangements and instability caused by LINE-1 retrotransposition"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8190-8568","authenticated-orcid":false,"given":"Carlos","family":"Mendez-Dorantes","sequence":"first","affiliation":[{"name":"Department of Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA;"},{"name":"Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA;"},{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA;"},{"name":"Division of Genetics and Genomics, Boston Children\u2019s Hospital, Boston, Massachusetts, 02115, USA;"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA;"},{"name":"Department of Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan, Hubei 430070, PRC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5041-2669","authenticated-orcid":false,"given":"Jennifer A.","family":"Karlow","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA;"},{"name":"Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA;"},{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;"},{"name":"Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Schofield","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serafina","family":"Turner","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;"},{"name":"Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Leventhal","sequence":"additional","affiliation":[{"name":"Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA;"},{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;"},{"name":"Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jupiter","family":"Kalinowski","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA;"},{"name":"School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PRC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Zumalave","sequence":"additional","affiliation":[{"name":"Mobile Genomes, Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela 15706, Spain"},{"name":"Instituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), Santiago de Compostela 15706, Spain"},{"name":"Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela 15782, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose M. 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