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Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

New England Journal of Medicine · 2012 · Vol. 366(10) · pp. 883–892

Marco Gerlinger✉(Barts Health NHS Trust)Andrew J. Rowan(Cancer Research UK)Stuart Horswell(Cancer Research UK)James Larkin(Royal Marsden Hospital)David Endesfelder(Cancer Research UK)Eva Grönroos(Cancer Research UK)Pierre Martinez(Cancer Research UK)Nicholas Matthews(Cancer Research UK)Grant D. Stewart(Cancer Research UK)Patrick Tarpey(Wellcome Sanger Institute)Ignacio Varela(Wellcome Sanger Institute)Benjamin Phillimore(Cancer Research UK)Sharmin Begum(Cancer Research UK)Neil Q. McDonald(Cancer Research UK)Adam Butler(Wellcome Sanger Institute)David Jones(Wellcome Sanger Institute)Keiran Raine(Wellcome Sanger Institute)Calli Latimer(Wellcome Sanger Institute)Cláudio R. Santos(Cancer Research UK)Mahrokh Nohadani(Royal Marsden Hospital)Aron C. Eklund(Technical University of Denmark)Bradley Spencer‐Dene(Cancer Research UK)Graham Clark(Cancer Research UK)Lisa Pickering(Royal Marsden Hospital)Gordon Stamp(Royal Marsden Hospital)Martin Gore(Royal Marsden Hospital)Zoltán Szállási(Harvard University)Julian Downward(Cancer Research UK)P. Andrew Futreal(Wellcome Sanger Institute)Charles Swanton(London Cancer)

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Abstract

Intratumor heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor-biopsy samples and may present major challenges to personalized-medicine and biomarker development. Intratumor heterogeneity, associated with heterogeneous protein function, may foster tumor adaptation and therapeutic failure through Darwinian selection. (Funded by the Medical Research Council and others.).

Cancer Genomics and Diagnostics Epigenetics and DNA Methylation RNA modifications and cancerComputational biologyEvolutionary biologyBiology

MeSH terms

EverolimusBiopsyCarcinoma, Renal CellChromosome AberrationsHumansImmunosuppressive AgentsKidneyKidney NeoplasmsMutationNeoplasm MetastasisPhenotypePhylogenyPloidiesBiomarkers, TumorSequence Analysis, DNA