Evidence map›Paper›PMID 27270107›Full record

ArticleNature genetics2016

Clonal evolution of glioblastoma under therapy.

Jiguang Wang, Emanuela Cazzato, Erik Ladewig, Veronique Frattini, Daniel I S Rosenbloom, Sakellarios Zairis, Francesco Abate, Zhaoqi Liu, Oliver Elliott, Yong-Jae Shin and 10 more

Open access · bronzeAbstract read
In one paragraph

Article in Nature genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 477 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
477citing papers in PubMed, 1 pooled it
45.8field-weighted citation impact, top 1% of its field
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

477 citing papers in PubMed, 1 synthesis or guideline pooled it, 783 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Review
  5. Accelerating discovery: Transformative clinical trial models in neuro-oncology.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Mechanisms, Microenvironments, and Models: Understanding Therapeutic Resistance in Glioblastoma.International journal of radiation oncology, biology, physics · 2026
    Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Review

417 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

20 authors at 5 institutions in 3 countries.

Jiguang WangDepartment of Systems Biology, Columbia University, New York, New York, USA.
Emanuela CazzatoFondazione IRCCS Istituto Neurologico Besta, Unit of Molecular Neuro-Oncology, Milan, Italy.
Erik LadewigDepartment of Systems Biology, Columbia University, New York, New York, USA.
Veronique FrattiniInstitute for Cancer Genetics, Columbia University, New York, New York, USA.
Daniel I S RosenbloomDepartment of Systems Biology, Columbia University, New York, New York, USA.ORCID 0000-0003-1413-3907
Sakellarios ZairisDepartment of Systems Biology, Columbia University, New York, New York, USA.
Francesco AbateDepartment of Systems Biology, Columbia University, New York, New York, USA.
Zhaoqi LiuDepartment of Systems Biology, Columbia University, New York, New York, USA.
Oliver ElliottDepartment of Systems Biology, Columbia University, New York, New York, USA.
Yong-Jae ShinDepartment of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Jin-Ku LeeDepartment of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
In-Hee LeeDepartment of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Woong-Yang ParkSamsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Marica EoliFondazione IRCCS Istituto Neurologico Besta, Unit of Molecular Neuro-Oncology, Milan, Italy.
Andrew J BlumbergDepartment of Mathematics, University of Texas, Austin, Texas, USA.
Anna LasorellaInstitute for Cancer Genetics, Columbia University, New York, New York, USA.
Do-Hyun NamDepartment of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Gaetano FinocchiaroFondazione IRCCS Istituto Neurologico Besta, Unit of Molecular Neuro-Oncology, Milan, Italy.
Antonio IavaroneInstitute for Cancer Genetics, Columbia University, New York, New York, USA.
Raul RabadanDepartment of Systems Biology, Columbia University, New York, New York, USA.
Columbia University · USSamsung Medical Center · KRCancer Genetics (United States) · USFondazione IRCCS Istituto Neurologico Carlo Besta · ITThe University of Texas at Austin · US

Funding

Training in Biomedical Informatics at Columbia UniversityT15LM007079 · NLM · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI NOEMIE ELHADAD, GEORGE M HRIPCSAK · 1992 to 2026
$28.9M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
Topology of Cancer Evolution and HeterogeneityU54CA193313 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI IAVARONE, ANTONIO, RABADAN, RAUL · 2015 to 2020
$10.4M
CELL, MOLECULAR AND DEVELOPMENTAL BIOLOGY OF CANCERT32CA009503 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI GAUTIER, JEAN · 1985 to 2016
$6.8M
The role of Id proteins in tumor development and angiogenesis in the brainR01CA101644 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LASORELLA, ANNA · 2003 to 2013
$3.5M
Computational analysis of Human High Grade GliomasR01NS061776 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI IAVARONE, ANTONIO · 2009 to 2013
$2.4M
Identification and modeling of driver genetic modules in glioblastomaR01CA179044 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI IAVARONE, ANTONIO, RABADAN, RAUL · 2014 to 2018
$2.3M
(PQB5) Reconstruction of Evolutionary Networks using Cross-Sectional Genomic DataR01CA185486 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LASORELLA, ANNA, RABADAN, RAUL · 2014 to 2017
$2.1M
The mechanisms driving brain oncogenesis by FGFR-TACC gene fusionsR01CA178546 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI IAVARONE, ANTONIO · 2014 to 2018
$1.8M
The Ureb-1 ubiquitin ligase in neural stem cells and cancerR01CA131126 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LASORELLA, ANNA · 2008 to 2012
$1.6M
Uncovering Evolutionary History using the Topology of Genomic Data with Applications to HIVR01GM117591 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI RABADAN, RAUL · 2015 to 2018
$1.3M
Clinical and Translational Science AwardTL1TR000082 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$732k
NCATS NIH HHS TL1 TR000082NCATS NIH HHS UL1 TR000040NCI NIH HHS R01 CA101644NCI NIH HHS R01 CA131126NCI NIH HHS R01 CA178546NCI NIH HHS R01 CA179044NCI NIH HHS R01 CA185486NCI NIH HHS T32 CA009503NCI NIH HHS U54 CA193313NIGMS NIH HHS R01 GM117591NINDS NIH HHS R01 NS061776NLM NIH HHS T15 LM007079
6 · The paper itself

Abstract

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. To better understand how GBM evolves, we analyzed longitudinal genomic and transcriptomic data from 114 patients. The analysis shows a highly branched evolutionary pattern in which 63% of patients experience expression-based subtype changes. The branching pattern, together with estimates of evolutionary rate, suggests that relapse-associated clones typically existed years before diagnosis. Fifteen percent of tumors present hypermutation at relapse in highly expressed genes, with a clear mutational signature. We find that 11% of recurrence tumors harbor mutations in LTBP4, which encodes a protein binding to TGF-β. Silencing LTBP4 in GBM cells leads to suppression of TGF-β activity and decreased cell proliferation. In recurrent GBM with wild-type IDH1, high LTBP4 expression is associated with worse prognosis, highlighting the TGF-β pathway as a potential therapeutic target in GBM.

Indexed as

Antineoplastic Agents, AlkylatingBiomarkers, TumorBrain NeoplasmsCell ProliferationClonal EvolutionDacarbazineDNA Modification MethylasesDNA Repair EnzymesGene Expression Regulation, NeoplasticGenomicsGlioblastomaHumansIsocitrate DehydrogenaseLatent TGF-beta Binding ProteinsLongitudinal StudiesMutationAntineoplastic Agents, AlkylatingBiomarkers, TumorDacarbazineDNA Modification MethylasesDNA Repair EnzymesIDH1 protein, humanIsocitrate DehydrogenaseLatent TGF-beta Binding ProteinsLTBP4 protein, humanMGMT protein, humanTemozolomideTransforming Growth Factor betaTumor Suppressor Proteins

Identifiers

PMID27270107
PMCPMC5627776
OpenAlexW2410468716

What OpenQuestion holds

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Read underepoch 390

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.