N
Nicholas Matthews
Researcher at London Research Institute
Publications - 5
Citations - 7890
Nicholas Matthews is an academic researcher from London Research Institute. The author has contributed to research in topics: Kinase activity & Genetic heterogeneity. The author has an hindex of 4, co-authored 5 publications receiving 7078 citations. Previous affiliations of Nicholas Matthews include Francis Crick Institute & Cancer Research UK.
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Journal ArticleDOI
Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.
Marco Gerlinger,Andrew Rowan,Stuart Horswell,James Larkin,David Endesfelder,Eva Grönroos,Pierre Martinez,Nicholas Matthews,Aengus Stewart,Patrick S. Tarpey,Ignacio Varela,Benjamin Phillimore,Sharmin Begum,Neil Q. McDonald,Adam Butler,David T. Jones,Keiran Raine,Calli Latimer,Claudio R. Santos,Mahrokh Nohadani,Aron Charles Eklund,Bradley Spencer-Dene,Graham Clark,Lisa Pickering,Gordon Stamp,Martin Gore,Zoltan Szallasi,Zoltan Szallasi,Julian Downward,P. Andrew Futreal,Charles Swanton +30 more
TL;DR: 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.
Journal ArticleDOI
Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing
Marco Gerlinger,Stuart Horswell,James Larkin,Andrew Rowan,Max Salm,Ignacio Varela,Rosalie Fisher,Nicholas McGranahan,Nicholas Matthews,Claudio R. Santos,Pierre Martinez,Benjamin Phillimore,Sharmin Begum,Adam Rabinowitz,Bradley Spencer-Dene,Sakshi Gulati,Paul A. Bates,Gordon Stamp,Lisa Pickering,Martin Gore,David Nicol,Steven Hazell,P. Andrew Futreal,Aengus Stewart,Charles Swanton,Charles Swanton +25 more
TL;DR: It was found that 73–75% of identified ccRCC driver aberrations were subclonal, confounding estimates of driver mutation prevalence, and the proportion of C>T transitions at CpG sites increased during tumor progression.
Journal ArticleDOI
BCL9L Dysfunction Impairs Caspase-2 Expression Permitting Aneuploidy Tolerance in Colorectal Cancer
Carlos López-García,Laurent Sansregret,Enric Domingo,Nicholas McGranahan,Sebastijan Hobor,Nicolai Juul Birkbak,Nicolai Juul Birkbak,Stuart Horswell,Eva Grönroos,Francesco Favero,Andrew Rowan,Nicholas Matthews,Sharmin Begum,Benjamin Phillimore,Rebecca A. Burrell,Dahmane Oukrif,Bradley Spencer-Dene,Michal Kovac,Gordon Stamp,Aengus Stewart,Håvard E. Danielsen,Marco Novelli,Ian Tomlinson,Charles Swanton,Charles Swanton +24 more
TL;DR: It is found that BCL9L dysfunction contributes to aneuploidy tolerance in both TP53-WT and mutant cells by reducing basal caspase-2 levels and preventing cleavage of MDM2 and BID.
Journal ArticleDOI
Cancer heterogeneity and “The Struggle for Existence”: Diagnostic and analytical challenges
TL;DR: The complexity induced by cases of ITH presents a considerable challenge for bioinformatics analyses and this is illustrated by describing the specific case of point mutation detection and a number of approaches which have been taken to combat these issues.
Proceedings ArticleDOI
Abstract 964: Intra-tumor heterogeneity and Darwinian selection revealed by multi-region exome sequencing of renal cell carcinomas
Marco Gerlinger,Andrew Rowan,Stuart Horswell,James Larkin,David Endesfelder,Eva Grönroos,Pierre Martinez,Nicholas Matthews,Aengus Stewart,Patrick S. Tarpey,Ignacio Varela,Benjamin Phillimore,Sharmin Begum,Neil Q. McDonald,Adam Butler,David T. Jones,Keiran Raine,Calli Latimer,Claudio R. Santos,Mahrokh Nohadani,Aron Charles Eklund,Bradley Spencer-Dene,Graham Clark,Lisa Pickering,Gordon Stamp,Martin Gore,Zoltan Szallasi,Julian Downward,P. Andrew Futreal,Charles Swanton +29 more
TL;DR: Genetic ITH was present in all tumors and occurs through spatially separated heterogeneous somatic mutations and chromosomal and ploidy aberrations leading to both, phenotypic intra-tumor diversity (mTOR activating mutation) and convergent loss of function(SETD2, PTEN and KDM5C).