Genomic footprints of activated telomere maintenance mechanisms in cancer

Sieverling, Lina; Hong, Chen; Koser, Sandra D.; Ginsbach, Philip; Kleinheinz, Kortine; Hutter, Barbara; Braun, Delia M.; Cortés-Ciriano, Isidro; Xi, Ruibin; Kabbe, Rolf; Park, Peter J.; Eils, Roland; Schlesner, Matthias; PCAWG Structural Variation Working Group; Brors, Benedikt; Rippe, Karsten; Jones, David T. W.; Feuerbach, Lars; PCAWG Consortium; Ossowski, Stephan; Estivill, Xavier, 1955-

Genomic footprints of activated telomere maintenance mechanisms in cancer

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dc.contributor.author Sieverling, Lina
dc.contributor.author Hong, Chen
dc.contributor.author Koser, Sandra D.
dc.contributor.author Ginsbach, Philip
dc.contributor.author Kleinheinz, Kortine
dc.contributor.author Hutter, Barbara
dc.contributor.author Braun, Delia M.
dc.contributor.author Cortés-Ciriano, Isidro
dc.contributor.author Xi, Ruibin
dc.contributor.author Kabbe, Rolf
dc.contributor.author Park, Peter J.
dc.contributor.author Eils, Roland
dc.contributor.author Schlesner, Matthias
dc.contributor.author PCAWG Structural Variation Working Group
dc.contributor.author Brors, Benedikt
dc.contributor.author Rippe, Karsten
dc.contributor.author Jones, David T. W.
dc.contributor.author Feuerbach, Lars
dc.contributor.author PCAWG Consortium
dc.contributor.author Ossowski, Stephan
dc.contributor.author Estivill, Xavier, 1955-
dc.date.accessioned 2022-05-20T05:52:19Z
dc.date.available 2022-05-20T05:52:19Z
dc.date.issued 2020
dc.description.abstract Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer.
dc.description.sponsorship The work was supported by grants from the German Federal Ministry of Education and Research (BMBF) within the e:Med program (project CancerTelSys, 01ZX1302 to K.R.) and the program for medical genome research (01KU1001A, -B, -C, and -D; 01KU1505A). S.D.K. received funding from the German Research Foundation (DFG) in research priority program SPP1463 (grant no. Br3535/1-2). I.C.C. has received funding from the European Union’s Framework Programme For Research and Innovation Horizon 2020 (2014–2020) under the Marie Sklodowska-Curie Grant Agreement No. 703543
dc.format.mimetype application/pdf
dc.identifier.citation Sieverling L, Hong C, Koser SD, Ginsbach P, Kleinheinz K, Hutter B et al. Genomic footprints of activated telomere maintenance mechanisms in cancer. Nat Commun. 2020 Feb 5;11(1):733. DOI:10.1038/s41467-019-13824-9
dc.identifier.doi http://dx.doi.org/10.1038/s41467-019-13824-9
dc.identifier.issn 2041-1723
dc.identifier.uri http://hdl.handle.net/10230/53180
dc.language.iso eng
dc.publisher Nature Research
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/703543
dc.rights © Lina Sieverling et al. 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject.other Càncer
dc.subject.other Tumors
dc.subject.other Telòmer
dc.subject.other Genòmica
dc.title Genomic footprints of activated telomere maintenance mechanisms in cancer
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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