Genomic footprints of activated telomere maintenance mechanisms in cancer
Creators: name: Hong, Chen
name: Koser, Sandra D.
name: Ginsbach, Philip
name: Kleinheinz, Kortine
name: Braun, Delia M.
name: Xi, Ruibin
name: Kabbe, Rolf
name: Eils, Roland
name: Schlesner, Matthias
name: Brors, Benedikt
name: Jones, David T. W.
name: Akdemir, Kadir C.
name: Alvarez, Eva G.
name: Baez-Ortega, Adrian
name: Beroukhim, Rameen
name: Boutros, Paul C.
name: Bowtell, David D. L.
name: Burns, Kathleen H.
name: Campbell, Peter J.
name: Chan, Kin
name: Chen, Ken
name: Cortés-Ciriano, Isidro
name: Dueso-Barroso, Ana
name: Dunford, Andrew J.
name: Edwards, Paul A.
name: Estivill, Xavier
name: Etemadmoghadam, Dariush
name: Feuerbach, Lars
name: Fink, J. Lynn
name: Frenkel-Morgenstern, Milana
name: Garsed, Dale W.
name: Gerstein, Mark
name: Gordenin, Dmitry A.
name: Haan, David
name: Haber, James E.
name: Hess, Julian M.
name: Hutter, Barbara
name: Imielinski, Marcin
name: Ju, Young Seok
name: Kazanov, Marat D.
name: Klimczak, Leszek J.
name: Koh, Youngil
name: Korbel, Jan O.
name: Kumar, Kiran
name: Lee, Eunjung Alice
name: Lee, Jake June-Koo
name: Li, Yilong
name: Lynch, Andy G.
name: Macintyre, Geoff
name: Markowetz, Florian
name: Martincorena, Iñigo
name: Martinez-Fundichely, Alexander
name: Meyerson, Matthew
name: Miyano, Satoru
name: Nakagawa, Hidewaki
name: Navarro, Fabio C. P.
name: Ossowski, Stephan
name: Park, Peter J.
name: Pearson, John V.
name: Puiggròs, Montserrat
name: Rippe, Karsten
name: Roberts, Nicola D.
name: Roberts, Steven A.
name: Rodriguez-Martin, Bernardo
name: Schumacher, Steven E.
name: Scully, Ralph
name: Shackleton, Mark
name: Sidiropoulos, Nikos
name: Sieverling, Lina
name: Stewart, Chip
name: Torrents, David
name: Tubio, Jose M. C.
name: Villasante, Izar
name: Waddell, Nicola
name: Wala, Jeremiah A.
name: Weischenfeldt, Joachim
name: Yang, Lixing
name: Yao, Xiaotong
name: Yoon, Sung-Soo
name: Zamora, Jorge
name: Zhang, Cheng-Zhong
Publisher: name: Apollo - University of Cambridge Repository
Year: 2020
Subjects: Article
/631/67/69
/631/114
/692/4028/67
/45
article

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.