Genomic footprints of activated telomere maintenance mechanisms in cancer

L Sieverling; C Hong; SD Koser; P Ginsbach; K Kleinheinz; B Hutter; DM Braun; I Cortés-Ciriano; R Xi; R Kabbe; PJ Park; R Eils; M Schlesner; K Rippe; DTW Jones; L Feuerbach; KC Akdemir; EG Alvarez; A Baez-Ortega; R Beroukhim; PC Boutros; DDL Bowtell; B Brors; KH Burns; PJ Campbell; K Chan; K Chen; A Dueso-Barroso; AJ Dunford; PA Edwards; X Estivill; D Etemadmoghadam; JL Fink; M Frenkel-Morgenstern; DW Garsed; M Gerstein; DA Gordenin; D Haan; JE Haber; JM Hess; M Imielinski; YS Ju; MD Kazanov; LJ Klimczak; Y Koh; JO Korbel; K Kumar; EA Lee; JJK Lee; Y Li; AG Lynch; G Macintyre; F Markowetz; I Martincorena; A Martinez-Fundichely; M Meyerson; S Miyano; H Nakagawa; FCP Navarro; S Ossowski; JV Pearson; M Puiggròs; ND Roberts; SA Roberts; B Rodriguez-Martin; SE Schumacher; R Scully; M Shackleton; N Sidiropoulos; C Stewart; D Torrents; JMC Tubio; I Villasante; N Waddell; JA Wala; J Weischenfeldt; L Yang; X Yao; SS Yoon; J Zamora; CZ Zhang

Journal article

Genomic footprints of activated telomere maintenance mechanisms in cancer

L Sieverling, C Hong, SD Koser, P Ginsbach, K Kleinheinz, B Hutter, DM Braun, I Cortés-Ciriano, R Xi, R Kabbe, PJ Park, R Eils, M Schlesner, K Rippe, DTW Jones, L Feuerbach, KC Akdemir, EG Alvarez, A Baez-Ortega, R Beroukhim Show all

Nature Communications | Published : 2020

DOI: 10.1038/s41467-019-13824-9

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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 o..

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University of Melbourne Researchers

David Bowtell Author

Dale Garsed Author

Oliver Hofmann Author

Heather Thorne Author

Grants

Awarded by Wellcome Trust

Funding Acknowledgements

We thank J. Kerssemakers, M. Prinz, and M. Heinold for their help in data processing. We thank I. Buchhalter for annotation of simple nucleotide variations. We thank D. Hubschmann for his support in correlation analysis. We thank all TelNet curators for sharing the results of their extensive literature research. We thank K.I. Deeg, P. Lichter, and S.M. Pfister for their support in early stages of the study. We thank I. Chung for comments and discussion. 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. We acknowledge the contributions of the many clinical networks across ICGC and TCGA who provided samples and data to the PCAWG Consortium, and the contributions of the Technical Working Group and the Germline Working Group of the PCAWG Consortium for collation, realignment, and harmonised variant calling of the cancer genomes used in this study. We thank the patients and their families for their participation in the individual ICGC and TCGA projects.