Evidence map›Paper›PMID 33051600›Full record

ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2021

Subependymal giant cell astrocytomas are characterized by mTORC1 hyperactivation, a very low somatic mutation rate, and a unique gene expression profile.

Krinio Giannikou, Zachary Zhu, Jaegil Kim, Kellen D Winden, Magdalena E Tyburczy, David Marron, Joel S Parker, Zachary Hebert, Anika Bongaarts, Len Taing and 20 more

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

Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

18 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
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  5. Article
  6. Review
  7. Solitary subependymal giant cell astrocytoma lacking TSC1/2 mutations and TTF-1 expression: A potential diagnostic pitfall.Neuropathology : official journal of the Japanese Society of Neuropathology · 2025
    Article
  8. Review
  9. Article
  10. iScience · 2023
    Article
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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

30 authors at 14 institutions in 3 countries.

Krinio GiannikouCancer Genetics Laboratory, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. kgiannikou@bwh.harvard.edu.
Zachary ZhuCancer Genetics Laboratory, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Jaegil KimBroad Institute of MIT and Harvard, Cancer Genome Program, Cambridge, MA, USA.
Kellen D WindenDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Magdalena E TyburczyCancer Genetics Laboratory, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
David MarronLineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Joel S ParkerLineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-2080-6901
Zachary HebertMolecular Biology Core Facility, Dana Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9401-2464
Anika BongaartsAmsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam, the Netherlands.
Len TaingCenter for Functional Cancer Epigenetics, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Henry W LongCenter for Functional Cancer Epigenetics, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
William V PisanoDepartment of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
Sanda AlexandrescuDepartment of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Brianna GodlewskiDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Mark NellistDepartment of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands.
Katarzyna KotulskaDepartment of Child Neurology, Medical University of Warsaw, Warsaw, Poland.
Sergiusz JozwiakDepartment of Child Neurology, Medical University of Warsaw, Warsaw, Poland.ORCID http://orcid.org/0000-0003-3350-6326
Marcin RoszkowskiDepartment of Neurosurgery, The Children's Memorial Health Institute, Warsaw, Poland.
Marek ManderaDepartment of Pediatric Neurosurgery, Medical University of Silesia, Katowice, Poland.ORCID http://orcid.org/0000-0003-2141-7932
Elizabeth A ThieleDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Hart LidovDepartment of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Gad GetzBroad Institute of MIT and Harvard, Cancer Genome Program, Cambridge, MA, USA.
Orrin DevinskyDepartment of Neurology, New York University School of Medicine, 223 E 34 Street, New York, NY, USA.
Michael S LawrenceBroad Institute of MIT and Harvard, Massachusetts General Hospital Cancer Center, Department of Pathology, Harvard Medical School, Charlestown, MA, USA.
Keith L LigonDepartment of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
David W EllisonDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Mustafa SahinDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7044-2953
Eleonora AronicaAmsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam, the Netherlands.
David M MeredithDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7054-8624
David J KwiatkowskiCancer Genetics Laboratory, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. dk@rics.bwh.harvard.edu.
Boston Children's Hospital · USBroad Institute · USBrigham and Women's Hospital · USDana-Farber Cancer Institute · USAmsterdam Neuroscience · NLHarvard University · USMedical University of Warsaw · PLUniversity of North Carolina at Chapel Hill · USChildren's Memorial Health Institute · PLErasmus University Rotterdam · NLMassachusetts General Hospital · USMedical University of Silesia · PLNew York University · USSt. Jude Children's Research Hospital · US

Funding

Strategies to Overcome Immune Resistance in Head and Neck CancersP01CA240239 · NCI · YALE UNIVERSITY · PI PAI, SARA ISABEL · 2019 to 2023
$8.4M
NCI NIH HHS P01 CA240239
6 · The paper itself

Abstract

Subependymal giant-cell astrocytomas (SEGAs) are slow-growing brain tumors that are a hallmark feature seen in 5-10% of patients with Tuberous Sclerosis Complex (TSC). Though histologically benign, they can cause serious neurologic symptoms, leading to death if untreated. SEGAs consistently show biallelic loss of TSC1 or TSC2. Herein, we aimed to define other somatic events beyond TSC1/TSC2 loss and identify potential transcriptional drivers that contribute to SEGA formation. Paired tumor-normal whole-exome sequencing was performed on 21 resected SEGAs from 20 TSC patients. Pathogenic variants in TSC1/TSC2 were identified in 19/21 (90%) SEGAs. Copy neutral loss of heterozygosity (size range: 2.2-46 Mb) was seen in 76% (16/21) of SEGAs (44% chr9q and 56% chr16p). An average of 1.4 other somatic variants (range 0-7) per tumor were identified, unlikely of pathogenic significance. Whole transcriptome RNA-sequencing analyses revealed 190 common differentially expressed genes in SEGA (n = 16, 13 from a prior study) in pairwise comparison to each of: low grade diffuse gliomas (n = 530) and glioblastoma (n = 171) from The Cancer Genome Atlas (TCGA) consortium, ganglioglioma (n = 10), TSC cortical tubers (n = 15), and multiple normal tissues. Among these, homeobox transcription factors (TFs) HMX3, HMX2, VAX1, SIX3; and TFs IRF6 and EOMES were all expressed >12-fold higher in SEGAs (FDR/q-value < 0.05). Immunohistochemistry supported the specificity of IRF6, VAX1, SIX3 for SEGAs in comparison to other tumor entities and normal brain. We conclude that SEGAs have an extremely low somatic mutation rate, suggesting that TSC1/TSC2 loss is sufficient to drive tumor growth. The unique and highly expressed SEGA-specific TFs likely reflect the neuroepithelial cell of origin, and may also contribute to the transcriptional and epigenetic state that enables SEGA growth following two-hit loss of TSC1 or TSC2 and mTORC1 activation.

Indexed as

AdolescentAstrocytomaBrain NeoplasmsChildChild, PreschoolFemaleHumansInfantMaleMechanistic Target of Rapamycin Complex 1Middle AgedMutation RateTranscriptomeTuberous Sclerosis Complex 1 ProteinTuberous Sclerosis Complex 2 ProteinYoung AdultMechanistic Target of Rapamycin Complex 1TSC1 protein, humanTSC2 protein, humanTuberous Sclerosis Complex 1 ProteinTuberous Sclerosis Complex 2 Protein

Identifiers

PMID33051600
PMCPMC9361192
OpenAlexW3092527178

What OpenQuestion holds

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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.