Evidence map›Paper›PMID 25650244›Full record

ArticleGenome research2015

Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution.

Hoon Kim, Siyuan Zheng, Seyed S Amini, Selene M Virk, Tom Mikkelsen, Daniel J Brat, Jonna Grimsby, Carrie Sougnez, Florian Muller, Jian Hu and 13 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 269 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
269citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

269 citing papers in PubMed, 1 synthesis or guideline pooled it, 429 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Accelerating discovery: Transformative clinical trial models in neuro-oncology.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
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  5. Immunotherapy for Glioma: A compartmental framework for resistance and rational combination design.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
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209 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors at 7 institutions in 1 country.

Hoon KimDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
Siyuan ZhengDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
Seyed S AminiDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
Selene M VirkCase Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA;
Tom MikkelsenDepartments of Neurology and Neurosurgery, Henry Ford Hospital, Detroit, Michigan 48202, USA;
Daniel J BratDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA;
Jonna GrimsbyThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;
Carrie SougnezThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;
Florian MullerDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
Jian HuDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
Andrew E SloanCase Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA; Brain Tumor and Neuro-oncology Center, Department of Neurosurgery, University Hospitals Case Medical Center, Case Western Reserve School of Medicine, Cleveland, Ohio 44106, USA;
Mark L CohenCase Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA; Department of Pathology, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA;
Erwin G Van MeirDepartment of Neurosurgery and Hematology and Medical Oncology, Winship Cancer Institute and School of Medicine, Emory University, Atlanta, Georgia 30322, USA;
Lisa ScarpaceDepartments of Neurology and Neurosurgery, Henry Ford Hospital, Detroit, Michigan 48202, USA;
Peter W LairdCenter for Epigenetics, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA;
John N WeinsteinDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
Eric S LanderThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;
Stacey GabrielThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;
Gad GetzThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;
Matthew MeyersonThe Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Lynda ChinDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
Jill S Barnholtz-SloanCase Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA;
Roel G W VerhaakDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; rverhaak@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USBroad Institute · USEmory University · USHenry Ford Hospital · USUniversity Hospitals Cleveland Medical Center · USUniversity School · USVan Andel Institute · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Winship Cancer Institute Cancer Center Support GrantP30CA138292 · NCI · EMORY UNIVERSITY · PI Suresh S Ramalingam · 2009 to 2026
$47.5M
Tropism Enhanced Oncolytic Adenovirus for the Treatment of Brain TumorsP50CA127001 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Juan Fueyo · 2008 to 2026
$41.2M
UNIVERSITY OF TEXAS MD ANDERSON SPORE IN OVARIAN CANCERP50CA083639 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BAST, ROBERT C · 1999 to 2015
$33.0M
QUANTITATION OF HUMAN BRAIN TUMOR THERAPY RESPONSE BY MRP01CA085878 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ROSS, BRIAN D. · 2001 to 2017
$31.9M
The USC-JHU Cancer Epigenome Characterization CenterU24CA143882 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BAYLIN, STEPHEN B., WEISENBERGER, DANIEL JOSEPH · 2009 to 2016
$13.3M
Integrative Pipeline for Analysis & Translational Application of TCGA Data (GDAC)U24CA143883 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI AKBANI, REHAN, MILLS, GORDON B. · 2009 to 2016
$10.6M
Genetic evolution of glioblastomas during radiation and temozolomide therapyR01CA188228 · NCI · DANA-FARBER CANCER INST · PI BEROUKHIM, RAMEEN, CHAKRAVARTI, ARNAB · 2015 to 2025
$6.9M
TRAINING IN COMPUTATIONAL GENOMIC EPIDEMIOLOGY OF CANCERR25CA094186 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI LI, LI · 2002 to 2016
$6.8M
THERAPEUTIC MODULATION OF ANGIOGENESIS IN HUMAN GLIOMASR01CA086335 · NCI · EMORY UNIVERSITY · PI VAN MEIR, ERWIN G. · 2000 to 2011
$3.9M
Defining mechanisms of extracellular communication for cancer therapyR01CA163722 · NCI · EMORY UNIVERSITY · PI VAN MEIR, ERWIN G. · 2013 to 2017
$1.7M
(PQ #4) Single cell barcoding for studies of study clonal evolution in glioblastomaR01CA190121 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SULMAN, ERIK, VERHAAK, ROEL GW · 2014 to 2017
$1.4M
NCI NIH HHS CA016672NCI NIH HHS CA143883NCI NIH HHS HHSN261201000057CNCI NIH HHS HHSN261201000057INCI NIH HHS P01 CA085878NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA138292NCI NIH HHS P50 CA083639NCI NIH HHS P50 CA083639-12NCI NIH HHS P50 CA127001NCI NIH HHS R01 CA086335NCI NIH HHS R01 CA163722NCI NIH HHS R01 CA188228NCI NIH HHS R01 CA190121NCI NIH HHS R25 CA094186NCI NIH HHS U24 CA143882NCI NIH HHS U24 CA143883PHS HHS HHSN261201000057C
6 · The paper itself

Abstract

Glioblastoma (GBM) is a prototypical heterogeneous brain tumor refractory to conventional therapy. A small residual population of cells escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence ∼ 7 mo after diagnosis. Understanding the molecular architecture of this residual population is critical for the development of successful therapies. We used whole-genome sequencing and whole-exome sequencing of multiple sectors from primary and paired recurrent GBM tumors to reconstruct the genomic profile of residual, therapy resistant tumor initiating cells. We found that genetic alteration of the p53 pathway is a primary molecular event predictive of a high number of subclonal mutations in glioblastoma. The genomic road leading to recurrence is highly idiosyncratic but can be broadly classified into linear recurrences that share extensive genetic similarity with the primary tumor and can be directly traced to one of its specific sectors, and divergent recurrences that share few genetic alterations with the primary tumor and originate from cells that branched off early during tumorigenesis. Our study provides mechanistic insights into how genetic alterations in primary tumors impact the ensuing evolution of tumor cells and the emergence of subclonal heterogeneity.

Indexed as

ExomeGenome, HumanHigh-Throughput Nucleotide SequencingAdultAgedAged, 80 and overAge FactorsBrain NeoplasmsClonal EvolutionDNA Copy Number VariationsDNA MethylationGenomicsGlioblastomaHumansMiddle AgedMutationTumor Suppressor Protein p53

Identifiers

PMID25650244
PMCPMC4352879
OpenAlexW2129418270

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LicenceCC BY-NC
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Registered trials

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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.