Evidence map›Paper›PMID 36049655›Full record

ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2022

A Knock-In Mouse Model of Thymoma With the GTF2I L424H Mutation.

Yongfeng He, In-Kyu Kim, Jing Bian, Alexander Polyzos, Dafne Campigli Di Giammartino, Yu-Wen Zhang, Ji Luo, Maria O Hernandez, Noemi Kedei, Maggie Cam and 17 more

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

Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 10% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Spontaneous Benign Thymoma in a 10-Week-Old Female ICR (CD-1) Mouse.Journal of the American Association for Laboratory Animal Science : JAALAS · 2025
    Article
  5. The influence of PD-L1 expression levels on the efficacy of combination therapy in thymic epithelial tumors.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors at 13 institutions in 2 countries.

Yongfeng HeSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
In-Kyu KimDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
Jing BianCCR Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Alexander PolyzosSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
Dafne Campigli Di GiammartinoSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
Yu-Wen ZhangDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia; New address: Department of Cell Biology, University of Virginia, School of Medicine, Charlottesville, Virginia.
Ji LuoLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Maria O HernandezCollaborative Protein Technology Resource, Office of Science and Technology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Noemi KedeiCollaborative Protein Technology Resource, Office of Science and Technology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Maggie CamCCR Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Alain C BorczukDepartment of Pathology, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York; New address: Department of Pathology, Northwell Health, Greenvale, New York.
Trevor LeeSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
Yumin HanSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
Elizabeth A ConnerCCR Genomics Core, National Cancer Institute, Bethesda, Maryland.
Madeline WongCCR Genomics Core, National Cancer Institute, Bethesda, Maryland.
Desiree C TilloCCR Genomics Core, National Cancer Institute, Bethesda, Maryland.
Shigeki UmemuraDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
Vincent ChenDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
Lydia RuanCCR Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Jessica B WhiteCaryl and Israel Englander Institute for Precision Medicine, New York-Presbyterian Hospital, Weill Cornell Medicine, New York, New York.
Ileana C MirandaLaboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, and The Rockefeller University, New York, New York.
Parirokh P AwasthiFrederick National Laboratory for Cancer Research, Laboratory Animal Sciences, Mouse Modeling & Cryopreservation, National Cancer Institute, Frederick, Maryland.
Nasser K AltorkiDepartment of Cardiothoracic Surgery, Weill Cornell Medicine, New York Presbyterian Hospital, New York, New York.
Prajan DivakarNanoString Technologies Inc., Seattle, Washington.
Olivier ElementoCaryl and Israel Englander Institute for Precision Medicine, New York-Presbyterian Hospital, Weill Cornell Medicine, New York, New York.
Effie ApostolouSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
Giuseppe GiacconeSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York; Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia. Electronic address: gig4001@med.cornell.edu.
National Cancer Institute · USCornell University · USWeill Cornell Medicine · USGeorgetown University · USOffice of Science · USCenter for Cancer Research · USGeorgetown University Medical Center · USNanostring Technologies (United States) · USNational Institutes of Health · USNew York Hospital Queens · USNewYork–Presbyterian Hospital · USPresbyterian Hospital · USRockefeller University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
New shRNA vectors for mammalian genetic analysisZIABC011304 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LUO, JI · 2010 to 2025
$2.4M
Intramural NIH HHS ZIA BC011304NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

introductionThe pathogenesis of thymic epithelial tumors remains largely unknown. We previously identified GTF2I L424H as the most frequently recurrent mutation in thymic epithelial tumors. Nevertheless, the precise role of this mutation in tumorigenesis of thymic epithelial cells is unclear.

methodsTo investigate the role of GTF2I L424H mutation in thymic epithelial cells in vivo, we generated and characterized a mouse model in which the Gtf2i L424H mutation was conditionally knocked-in in the Foxn1+ thymic epithelial cells. Digital spatial profiling was performed on thymomas and normal thymic tissues with GeoMx-mouse whole transcriptome atlas. Immunohistochemistry staining was performed using both mouse tissues and human thymic epithelial tumors.

resultsWe observed that the Gtf2i mutation impairs development of the thymic medulla and maturation of medullary thymic epithelial cells in young mice and causes tumor formation in the thymus of aged mice. Cell cycle-related pathways, such as E2F targets and MYC targets, are enriched in the tumor epithelial cells. Results of gene set variation assay analysis revealed that gene signatures of cortical thymic epithelial cells and thymic epithelial progenitor cells are also enriched in the thymomas of the knock-in mice, which mirrors the human counterparts in The Cancer Genome Atlas database. Immunohistochemistry results revealed similar expression pattern of epithelial cell markers between mouse and human thymomas.

conclusionsWe have developed and characterized a novel thymoma mouse model. This study improves knowledge of the molecular drivers in thymic epithelial cells and provides a tool for further study of the biology of thymic epithelial tumors and for development of novel therapies.

Indexed as

Neoplasms, Glandular and EpithelialThymomaThymus NeoplasmsTranscription Factors, TFIITranscription Factors, TFIIIAnimalsHumansMiceMutationGTF2I protein, humanGtf2i protein, mouseTranscription Factors, TFIITranscription Factors, TFIIIDigital spatial profilingGTF2I mutationMouse modelThymic epithelial tumors

Identifiers

PMID36049655
PMCPMC9691559
OpenAlexW4293522434

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.