ArticleCell2021
Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes.
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Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 352 papers, 1 of them a synthesis that pooled it.
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352citing papers in PubMed, 1 pooled it
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Who cites it
352 citing papers in PubMed, 1 synthesis or guideline pooled it, 533 citations in OpenAlex.
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- Gene mutant dosage is associated with prognosis and metastatic tropism in 60,000 clinical cancer samples.Nature genetics · 2026Article
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- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Breast cancer genomic subtype-specific copy number alterations in metastases.Scientific reports · 2026Article
- Personalized reference genome-based pipeline reveals comprehensive haplotype-resolved views of cancer genomes.bioRxiv : the preprint server for biology · 2026Article
292 more citing papers are in PubMed but not listed here.
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Authors and funding
50 authors at 20 institutions in 7 countries.
Stefan C DentroCancer Genomics Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK; Big Data Institute, University of Oxford, Oxford OX3 7LF, UK.
Ignaty LeshchinerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Kerstin HaaseCancer Genomics Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
Maxime TarabichiCancer Genomics Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
Jeff WintersingerUniversity of Toronto, Toronto, ON M5S 3E1, Canada; Vector Institute, Toronto, ON M5G 1L7, Canada.
Amit G DeshwarUniversity of Toronto, Toronto, ON M5S 3E1, Canada; Vector Institute, Toronto, ON M5G 1L7, Canada.
Kaixian YuThe University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yulia RubanovaUniversity of Toronto, Toronto, ON M5S 3E1, Canada; Vector Institute, Toronto, ON M5G 1L7, Canada.
Geoff MacintyreCancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
Jonas DemeulemeesterCancer Genomics Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Department of Human Genetics, University of Leuven, 3000 Leuven, Belgium.
Ignacio Vázquez-GarcíaWellcome Trust Sanger Institute, Cambridge CB10 1SA, UK; University of Cambridge, Cambridge CB2 0QQ, UK; Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Irving Institute for Cancer Dynamics, Columbia University, New York, NY 10027, USA.
Kortine KleinheinzGerman Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Heidelberg University, 69120 Heidelberg, Germany.
Dimitri G LivitzBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Salem MalikicCancer Data Science Laboratory, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Nilgun DonmezSimon Fraser University, Burnaby, BC V5A 1S6, Canada; Vancouver Prostate Centre, Vancouver, BC V6H 3Z6, Canada.
Subhajit SenguptaNorthShore University HealthSystem, Evanston, IL 60201, USA.
Pavana AnurMolecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97231, USA.
Clemency JollyCancer Genomics Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
Marek CmeroUniversity of Melbourne, Melbourne, VIC 3010, Australia; Walter + Eliza Hall Institute, Melbourne, VIC 3000, Australia.
Daniel RosebrockBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Steven E SchumacherBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Yu FanThe University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Matthew FittallCancer Genomics Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
Ruben M DrewsCancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
Xiaotong YaoWeill Cornell Medicine, New York, NY 10065, USA; New York Genome Center, New York, NY 10013, USA.
Thomas B K WatkinsCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
Juhee LeeUniversity of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Matthias SchlesnerGerman Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Hongtu ZhuThe University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
David J AdamsWellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
Nicholas McGranahanCancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London WC1E 6BT, UK; Cancer Genome Evolution Research Group, University College London Cancer Institute, London WC1E 6DD, UK.
Charles SwantonCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London WC1E 6BT, UK; Department of Medical Oncology, University College London Hospitals, London NW1 2BU, UK.
Gad GetzBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Massachusetts General Hospital Center for Cancer Research, Charlestown, MA 02129, USA; Massachusetts General Hospital, Department of Pathology, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02215, USA.
Paul C BoutrosUniversity of Toronto, Toronto, ON M5S 3E1, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; University of California, Los Angeles, Los Angeles, CA 90095, USA.
Marcin ImielinskiWeill Cornell Medicine, New York, NY 10065, USA; New York Genome Center, New York, NY 10013, USA.
Rameen BeroukhimBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Dana-Farber Cancer Institute, Boston, MA 02215, USA.
S Cenk SahinalpCancer Data Science Laboratory, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Yuan JiNorthShore University HealthSystem, Evanston, IL 60201, USA; The University of Chicago, Chicago, IL 60637, USA.
Martin PeiferDepartment of Translational Genomics, Center for Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
Inigo MartincorenaWellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
Florian MarkowetzCancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
Ville MustonenOrganismal and Evolutionary Biology Research Programme, Department of Computer Science, Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland.
Ke YuanCancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK; School of Computing Science, University of Glasgow, Glasgow G12 8RZ, UK.
Moritz GerstungWellcome Trust Sanger Institute, Cambridge CB10 1SA, UK; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge CB10 1SD, UK; European Molecular Biology Laboratory, Genome Biology Unit, 69117 Heidelberg, Germany.
Paul T SpellmanMolecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97231, USA.
Wenyi WangThe University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Quaid D MorrisUniversity of Toronto, Toronto, ON M5S 3E1, Canada; Vector Institute, Toronto, ON M5G 1L7, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Computational and Systems Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
David C WedgeBig Data Institute, University of Oxford, Oxford OX3 7LF, UK; Oxford NIHR Biomedical Research Centre, Oxford OX4 2PG, UK; Manchester Cancer Research Centre, University of Manchester, Manchester M20 4GJ, UK.
Peter Van LooCancer Genomics Laboratory, The Francis Crick Institute, London NW1 1AT, UK. Electronic address: peter.vanloo@crick.ac.uk.
PCAWG Evolution and Heterogeneity Working Group and the PCAWG Consortium
Broad Institute · USWellcome Sanger Institute · GBThe University of Texas MD Anderson Cancer Center · USGenomics (United Kingdom) · GBThe Francis Crick Institute · GBUniversity of Toronto · CACancer Research UK · GBNational Cancer Institute · USOregon Health & Science University · USUniversity of Cambridge · GBGerman Cancer Research Center · DENorthShore University HealthSystem · USOntario Institute for Cancer Research · CASimon Fraser University · CAUniversity of Cologne · DEUniversity of Helsinki · FIWeill Cornell Medicine · USDana-Farber Cancer Institute · USMassachusetts General Hospital · USOxford BioMedica (United Kingdom) · GB
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MTumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8MUCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2MTumor evolution and intratumor heterogeneityZIABC011987 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SAHINALP, SULEYMAN · 2020 to 2025
$6.6MTCGA Data Analysis Center at BerkeleyU24CA143799 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI SPEED, TERENCE PAUL, SPELLMAN, PAUL T. · 2009 to 2016
$4.9MGlobal Infrastructure for Collaborative High-throughput Cancer Genomics AnalysisU24CA210999 · NCI · BROAD INSTITUTE, INC. · PI GETZ, GAD A · 2016 to 2020
$4.7MOHSU Center for Specialized Data Analysis as part of the GDANU24CA210957 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI DEMIR, EMEK, SPELLMAN, PAUL T. · 2016 to 2020
$2.2MBayesian models for cancer prognosis by integrating diverse types of dataR01CA132897 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI JI, YUAN, MUELLER, PETER · 2008 to 2019
$2.1MStatistical methods for genomic analysis of heterogeneous tumorsR01CA183793 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WANG, WENYI · 2014 to 2018
$1.7MStatistical methods and tools for cancer risk prediction in families with germline mutations in TP53R01CA239342 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WANG, WENYI · 2019 to 2022
$1.5MCancer Research UK 21717Cancer Research UK 21777Cancer Research UK 24956Cancer Research UK 27176Cancer Research UK FC001169Cancer Research UK FC001202Medical Research Council FC001169Medical Research Council FC001202Medical Research Council MR/L016311/1Medical Research Council MR/V000292/1NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA211015NCI NIH HHS R01 CA132897NCI NIH HHS R01 CA183793NCI NIH HHS R01 CA239342NCI NIH HHS U24 CA143799NCI NIH HHS U24 CA210957NCI NIH HHS U24 CA210999Wellcome Trust 211179/Z/18/ZWellcome Trust FC001169Wellcome Trust FC001202Wellcome Trust WT097678
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.
Indexed as
Genetic HeterogeneityDatabases, GeneticDNA Copy Number VariationsDNA, NeoplasmDrug Resistance, NeoplasmHumansNeoplasmsPolymorphism, Single NucleotideWhole Genome SequencingDNA, Neoplasmbranching evolutioncancer driver genescancer evolutionintra-tumor heterogeneitypan-cancer genomicssubclonal reconstructiontumor phylogenywhole-genome sequencing
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.