Evidence map›Paper›PMID 31992716›Full record

ArticleNature communications2020

Longitudinal assessment of tumor development using cancer avatars derived from genetically engineered pluripotent stem cells.

Tomoyuki Koga, Isaac A Chaim, Jorge A Benitez, Sebastian Markmiller, Alison D Parisian, Robert F Hevner, Kristen M Turner, Florian M Hessenauer, Matteo D'Antonio, Nam-Phuong D Nguyen and 11 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing 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

43 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  16. Biomaterial-basedCancer pathogenesis and therapy · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Tomoyuki Koga *Ludwig Cancer Research San Diego Branch, 9500 Gilman Dr., CMM-East Room 3055, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0002-8330-117X
Isaac A Chaim *Department of Cellular and Molecular Medicine, University of California San Diego, 2880 Torrey Pines Scenic Drive, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0003-1787-046X
Jorge A BenitezLudwig Cancer Research San Diego Branch, 9500 Gilman Dr., CMM-East Room 3055, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0003-3185-9056
Sebastian MarkmillerDepartment of Cellular and Molecular Medicine, University of California San Diego, 2880 Torrey Pines Scenic Drive, La Jolla, CA, 92093, USA.
Alison D ParisianLudwig Cancer Research San Diego Branch, 9500 Gilman Dr., CMM-East Room 3055, La Jolla, CA, 92093, USA.
Robert F HevnerDepartment of Pathology, University of California San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA.
Kristen M TurnerLudwig Cancer Research San Diego Branch, 9500 Gilman Dr., CMM-East Room 3055, La Jolla, CA, 92093, USA.
Florian M HessenauerLudwig Cancer Research San Diego Branch, 9500 Gilman Dr., CMM-East Room 3055, La Jolla, CA, 92093, USA.
Matteo D'AntonioInstitute for Genomic Medicine, University of California San Diego, 9500 Gilman Dr. Mail Code 0761, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0001-5844-6433
Nam-Phuong D NguyenDepartment of Computer Science and Engineering, University of California San Diego, 9500 Gilman Dr., Mail Code 0404, La Jolla, CA, 92093, USA.
Shahram SaberiDepartment of Neuroscience, University of California San Diego, 9500 Gilman Dr., Mail Code 0662, La Jolla, CA, 92093, USA.
Jianhui MaLudwig Cancer Research San Diego Branch, 9500 Gilman Dr., CMM-East Room 3055, La Jolla, CA, 92093, USA.
Shunichiro MikiLudwig Cancer Research San Diego Branch, 9500 Gilman Dr., CMM-East Room 3055, La Jolla, CA, 92093, USA.
Antonia D BoyerLudwig Cancer Research San Diego Branch, 9500 Gilman Dr., CMM-East Room 3055, La Jolla, CA, 92093, USA.
John RavitsDepartment of Neuroscience, University of California San Diego, 9500 Gilman Dr., Mail Code 0662, La Jolla, CA, 92093, USA.
Kelly A FrazerInstitute for Genomic Medicine, University of California San Diego, 9500 Gilman Dr. Mail Code 0761, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0002-6060-8902
Vineet BafnaDepartment of Computer Science and Engineering, University of California San Diego, 9500 Gilman Dr., Mail Code 0404, La Jolla, CA, 92093, USA.
Clark C ChenDepartment of Neurosurgery, University of Minnesota, 420 Delaware St SE, Minneapolis, MN, 55455, USA.
Paul S MischelLudwig Cancer Research San Diego Branch, 9500 Gilman Dr., CMM-East Room 3055, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0002-4560-2211
Gene W YeoDepartment of Cellular and Molecular Medicine, University of California San Diego, 2880 Torrey Pines Scenic Drive, La Jolla, CA, 92093, USA. geneyeo@ucsd.edu.
Frank B FurnariLudwig Cancer Research San Diego Branch, 9500 Gilman Dr., CMM-East Room 3055, La Jolla, CA, 92093, USA. ffurnari@ucsd.edu.ORCID http://orcid.org/0000-0003-1909-4361

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
UCSD/SDSU IRACDAK12GM068524 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TREJO, JOANN · 2003 to 2025
$24.4M
Training Program in Basic Clinical GeneticsT32GM008666 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMILTON, BRUCE A · 1998 to 2021
$8.6M
Genotypic Interactions in Brain Cancer HeterogeneityR01NS080939 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FURNARI, FRANK · 2012 to 2022
$3.5M
The role of mTORC2 in reprogramming cancer cell metabolismR01NS073831 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MISCHEL, PAUL S · 2011 to 2020
$3.4M
Reconstruction of cardiovascular regulatory networks from large-scale single-cell analyses of cardiovascular lineagesR01HD085902 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C, YEO, EUGENE WEI-MING · 2016 to 2020
$3.1M
Computational methods for detecting patterns of complex genomic variationR01GM114362 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Vineet Bafna · 2016 to 2026
$3.1M
UC San Diego Genetics Training ProgramT32GM145427 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRUCE A HAMILTON · 2022 to 2026
$2.6M
Analysis of RNA binding proteins directing hematopoietic stem cell fateR01HL137223 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HOPE, KRISTIN, YEO, EUGENE WEI-MING · 2018 to 2021
$2.5M
NCI NIH HHS P30 CA023100NHLBI NIH HHS R01 HL137223NICHD NIH HHS R01 HD085902NIGMS NIH HHS K12 GM068524NIGMS NIH HHS R01 GM114362NIGMS NIH HHS T32 GM008666NIGMS NIH HHS T32 GM145427NINDS NIH HHS R01 NS073831NINDS NIH HHS R01 NS080939
6 · The paper itself

Abstract

Many cellular models aimed at elucidating cancer biology do not recapitulate pathobiology including tumor heterogeneity, an inherent feature of cancer that underlies treatment resistance. Here we introduce a cancer modeling paradigm using genetically engineered human pluripotent stem cells (hiPSCs) that captures authentic cancer pathobiology. Orthotopic engraftment of the neural progenitor cells derived from hiPSCs that have been genome-edited to contain tumor-associated genetic driver mutations revealed by The Cancer Genome Atlas project for glioblastoma (GBM) results in formation of high-grade gliomas. Similar to patient-derived GBM, these models harbor inter-tumor heterogeneity resembling different GBM molecular subtypes, intra-tumor heterogeneity, and extrachromosomal DNA amplification. Re-engraftment of these primary tumor neurospheres generates secondary tumors with features characteristic of patient samples and present mutation-dependent patterns of tumor evolution. These cancer avatar models provide a platform for comprehensive longitudinal assessment of human tumor development as governed by molecular subtype mutations and lineage-restricted differentiation.

Indexed as

Genetic EngineeringAnimalsBrain NeoplasmsCell DifferentiationCell Line, TumorFemaleGene Expression Regulation, NeoplasticGenomeGlioblastomaGliomaHumansMiceMice, SCIDMutationNeoplasm TransplantationNeoplastic Stem CellsNeurofibromin 1NF1 protein, humanPTEN PhosphohydrolasePTEN protein, humanTrp53 protein, mouseTumor Suppressor Protein p53

Identifiers

PMID31992716
PMCPMC6987220

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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.