Dentro, Stefan C., Leshchiner, Ignaty, Haase, Kerstin, Tarabichi, Maxime, Wintersinger, Jeff, Deshwar, Amit G., Yu, Kaixian, Rubanova, Yulia, Macintyre, Geoff, Demeulemeester, Jonas ORCID: 0000-0002-2660-2478, Vazquez-Garcia, Ignacio, Kleinheinz, Kortine, Livitz, Dimitri G., Malikic, Salem ORCID: 0000-0002-4215-5655, Donmez, Nilgun, Sengupta, Subhajit, Anur, Pavana, Jolly, Clemency, Cmero, Marek, Rosebrock, Daniel ORCID: 0000-0002-4818-4983, Schumacher, Steven E., Fan, Yu, Fittall, Matthew, Drews, Ruben M., Yao, Xiaotong, Watkins, Thomas B. K., Lee, Juhee, Schlesner, Matthias, Zhu, Hongtu, Adams, David J., McGranahan, Nicholas ORCID: 0000-0001-9537-4045, Swanton, Charles ORCID: 0000-0002-4299-3018, Getz, Gad, Boutros, Paul C., Imielinski, Marcin, Beroukhim, Rameen, Sahinalp, S. Cenk, Ji, Yuan, Peifer, Martin, Martincorena, Inigo ORCID: 0000-0003-1122-4416, Markowetz, Florian, Mustonen, Ville ORCID: 0000-0002-7270-1792, Yuan, Ke, Gerstung, Moritz ORCID: 0000-0001-6709-963X, Spellman, Paul T., Wang, Wenyi, Morris, Quaid D., Wedge, David C. and Van Loo, Peter (2021). Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes. Cell, 184 (8). S. 2239 - 2294. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Dentro, Stefan C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leshchiner, IgnatyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haase, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tarabichi, MaximeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wintersinger, JeffUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deshwar, Amit G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yu, KaixianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rubanova, YuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Macintyre, GeoffUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Demeulemeester, JonasUNSPECIFIEDorcid.org/0000-0002-2660-2478UNSPECIFIED
Vazquez-Garcia, IgnacioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kleinheinz, KortineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Livitz, Dimitri G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Malikic, SalemUNSPECIFIEDorcid.org/0000-0002-4215-5655UNSPECIFIED
Donmez, NilgunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sengupta, SubhajitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anur, PavanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jolly, ClemencyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cmero, MarekUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosebrock, DanielUNSPECIFIEDorcid.org/0000-0002-4818-4983UNSPECIFIED
Schumacher, Steven E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fan, YuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fittall, MatthewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drews, Ruben M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yao, XiaotongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Watkins, Thomas B. K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, JuheeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlesner, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhu, HongtuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adams, David J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McGranahan, NicholasUNSPECIFIEDorcid.org/0000-0001-9537-4045UNSPECIFIED
Swanton, CharlesUNSPECIFIEDorcid.org/0000-0002-4299-3018UNSPECIFIED
Getz, GadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boutros, Paul C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Imielinski, MarcinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beroukhim, RameenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sahinalp, S. CenkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ji, YuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peifer, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martincorena, InigoUNSPECIFIEDorcid.org/0000-0003-1122-4416UNSPECIFIED
Markowetz, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mustonen, VilleUNSPECIFIEDorcid.org/0000-0002-7270-1792UNSPECIFIED
Yuan, KeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerstung, MoritzUNSPECIFIEDorcid.org/0000-0001-6709-963XUNSPECIFIED
Spellman, Paul T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, WenyiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morris, Quaid D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wedge, David C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Van Loo, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-607844
DOI: 10.1016/j.cell.2021.03.009
Journal or Publication Title: Cell
Volume: 184
Number: 8
Page Range: S. 2239 - 2294
Date: 2021
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4172
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
COPY-NUMBER ANALYSIS; MUTATIONAL SIGNATURES; PREDICTS PROGRESSION; EVOLUTIONARY HISTORY; VARIABLE SELECTION; DENSITY-ESTIMATION; SOMATIC MUTATIONS; CLONAL EVOLUTION; RB1 GENE; INFERENCEMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60784

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