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Characterizinggenetic intra-tumorheterogeneity across2,658 human cancergenomes Stefan C. DentroIgnaty LeshchinerKerstin Haase2021 год

Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes
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Аннотация: Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin, and drivers of ITH across cancer types are poorly understood. To address this, we extensively characterize ITH across whole-genome sequences of 2,658 cancer samples spanning 38 cancer types. Nearly all informative samples (95.1%) contain evidence of distinct subclonal expansions with frequent branching relationships between subclones. We observe positive selection of subclonal driver mutations across most cancer types and identify cancer type-specific subclonal patterns of driver gene mutations, fusions, structural variants, and copy number alterations as well as dynamic changes in mutational processes between subclonal expansions. Our results underline the importance of ITH and its drivers in tumor evolution and provide a pan-cancer resource of comprehensively annotated subclonal events from whole-genome sequencing data.
Год издания: 2021
Авторы: Stefan C. Dentro, Ignaty Leshchiner, Kerstin Haase, Maxime Tarabichi, Jeff Wintersinger, Amit G. Deshwar, Kaixian Yu, Yulia Rubanova, Geoff Macintyre, Jonas Demeulemeester, Ignacio Vázquez-Garćıa, Kortine Kleinheinz, Dimitri Livitz, Salem Malikić, Nilgun Donmez, Subhajit Sengupta, Pavana Anur, Clemency Jolly, Marek Cmero, Daniel Rosebrock, Steven E. Schumacher, Yu Fan, Matthew W. Fittall, Ruben M. Drews, Xiaotong Yao, Thomas B.K. Watkins, Ju‐Hee Lee, Matthias Schlesner, Hongtu Zhu, David J. Adams, Nicholas McGranahan, Charles Swanton, Gad Getz, Paul C. Boutros, Marcin Imieliński, Rameen Beroukhim, S. Cenk Şahinalp, Yuan Ji, Martin Peifer, Iñigo Martincorena, Florian Markowetz, Ville Mustonen, Ke Yuan, Moritz Gerstung, Paul T. Spellman, Wenyi Wang, Quaid Morris, David C. Wedge, Peter Van Loo, Stefan C. Dentro, Ignaty Leshchiner, Moritz Gerstung, Clemency Jolly, Kerstin Haase, Maxime Tarabichi, Jeff Wintersinger, Amit G. Deshwar, Kaixian Yu, Santiago González, Yulia Rubanova, Geoff Macintyre, Jonas Demeulemeester, David J. Adams, Pavana Anur, Rameen Beroukhim, Paul C. Boutros, David D.L. Bowtell, Peter J. Campbell, Shaolong Cao, Elizabeth L. Christie, Marek Cmero, Yupeng Cun, Kevin J. Dawson, Nilgun Donmez, Ruben M. Drews, Roland Eils, Yu Fan, Matthew W. Fittall, Dale W. Garsed, Gad Getz, Gavin Ha, Marcin Imieliński, Lara Jerman, Yuan Ji, Kortine Kleinheinz, Juhee Lee, Henry Lee-Six, Dimitri Livitz, Salem Malikić, Florian Markowetz, Iñigo Martincorena, Thomas J. Mitchell, Ville Mustonen, Layla Oesper, Martin Peifer, Myron Peto, Benjamin J. Raphael, Daniel Rosebrock, S. Cenk Şahinalp, Adriana Salcedo, Matthias Schlesner, Steven E. Schumacher, Subhajit Sengupta, Ruian Shi, Seung Jun Shin, Lincoln Stein, Oliver Spiro, Ignacio Vázquez-Garćıa, Shankar Vembu, David A. Wheeler, Tsun-Po Yang, Xiaotong Yao, Ke Yuan, Hongtu Zhu, Wenyi Wang, Quaid Morris, Paul T. Spellman, David C. Wedge, Peter Van Loo
Издательство: Cell Press
Источник: Cell
Ключевые слова: Cancer Genomics and Diagnostics, Evolution and Genetic Dynamics, Genomics and Rare Diseases
Другие ссылки: Cell (PDF)
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OPUS (Augsburg University) (PDF)
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UCL Discovery (University College London) (PDF)
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OPAL (Open@LaTrobe) (La Trobe University) (PDF)
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Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (HTML)
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Lirias (KU Leuven) (PDF)
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bioRxiv (Cold Spring Harbor Laboratory) (HTML)
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