The epidermal growth factor receptor variant type III mutation frequently found in gliomas induces astrogenesis in human cerebral organoids

Kim, Hyun-Mun; Lee, Sang-Hyeok; Lim, Jaejoon; Yoo, Jongman; Hwang, Deuk-Soo

doi:10.1111/cpr.12965

Cited by 13 publications

(7 citation statements)

References 23 publications

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“…An increased frequency of mutations in EGFR, PTEN, ZNF429, and CHEK2 was instead primarily found in IDH1-wildtype patients. Mutations in EGFR are commonly found in glioblastoma and promote astrogenesis [ 92 ]. Mutations or deletions of PTEN have also been identified in glioblastoma and affect the same signaling network as EGFR mutations [ 4 ].…”

Section: Resultsmentioning

confidence: 99%

A Genome-Wide Profiling of Glioma Patients with an IDH1 Mutation Using the Catalogue of Somatic Mutations in Cancer Database

Pappula

Rasheed

Mirzaei

et al. 2021

Cancers

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Gliomas are differentiated into two major disease subtypes, astrocytoma or oligodendroglioma, which are then characterized as either IDH (isocitrate dehydrogenase)-wild type or IDH-mutant due to the dramatic differences in prognosis and overall survival. Here, we investigated the genetic background of IDH1-mutant gliomas using the Catalogue of Somatic Mutations in Cancer (COSMIC) database. In astrocytoma patients, we found that IDH1 is often co-mutated with TP53, ATRX, AMBRA1, PREX1, and NOTCH1, but not CHEK2, EGFR, PTEN, or the zinc finger transcription factor ZNF429. The majority of the mutations observed in these genes were further confirmed to be either drivers or pathogenic by the Cancer-Related Analysis of Variants Toolkit (CRAVAT). Gene expression analysis showed down-regulation of DRG2 and MSN expression, both of which promote cell proliferation and invasion. There was also significant over-expression of genes such as NDRG3 and KCNB1 in IDH1-mutant astrocytoma patients. We conclude that IDH1-mutant glioma is characterized by significant genetic changes that could contribute to a better prognosis in glioma patients.

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Section: Resultsmentioning

confidence: 99%

A Genome-Wide Profiling of Glioma Patients with an IDH1 Mutation Using the Catalogue of Somatic Mutations in Cancer Database

Pappula

Rasheed

Mirzaei

et al. 2021

Cancers

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“…The EGFRvIII-mutated organoids are larger, retain more astrocytes, and have higher Ki67 expression than wild-type organoids, thus suggesting that EGFRvIII mutation enhances cell proliferation. EGFRvIII- organoids show significantly increased apoptotic cell death after TMZ treatment, thus indicating that this model can also be applied to evaluate anti-GBM drugs 48 . In addition, GBOs have essential applications in studying glioma cell niche microenvironments.…”

Section: Application Of Organoids In Gbm Researchmentioning

confidence: 99%

Development of glioblastoma organoids and their applications in personalized therapy

et al. 2023

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Glioblastomas (GBMs) are the brain tumors with the highest malignancy and poorest prognoses. GBM is characterized by high heterogeneity and resistance to drug treatment. Organoids are 3-dimensional cultures that are constructed in vitro and comprise cell types highly similar to those in organs or tissues in vivo, thus simulating specific structures and physiological functions of organs. Organoids have been technically developed into an advanced ex vivo disease model used in basic and preclinical research on tumors. Brain organoids, which simulate the brain microenvironment while preserving tumor heterogeneity, have been used to predict patients’ therapeutic responses to antitumor drugs, thus enabling a breakthrough in glioma research. GBM organoids provide an effective supplementary model that reflects human tumors’ biological characteristics and functions in vitro more directly and accurately than traditional experimental models. Therefore, GBM organoids are widely applicable in disease mechanism research, drug development and screening, and glioma precision treatments. This review focuses on the development of various GBM organoid models and their applications in identifying new individualized therapies against drug-resistant GBM.

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“…To date, several EGFR variants have been studied in humans [ 36 , 37 , 38 ]. In addition to the full-length isoform (isoform A), cells can also produce alternate EGFR isoforms that lack the intracellular domain [ 39 ].…”

Section: Genetic Characterization and Comparison Of Xmrk With The Human Egfrmentioning

confidence: 99%

Xmrks the Spot: Fish Models for Investigating Epidermal Growth Factor Receptor Signaling in Cancer Research

Monroe

Basheer

Gibert

2021

Cells

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Studies conducted in several fish species, e.g., Xiphophorus hellerii (green swordtail) and Xiphophorus maculatus (southern platyfish) crosses, Oryzias latipes (medaka), and Danio rerio (zebrafish), have identified an oncogenic role for the receptor tyrosine kinase, Xmrk, a gene product closely related to the human epidermal growth factor receptor (EGFR), which is associated with a wide variety of pathological conditions, including cancer. Comparative analyses of Xmrk and EGFR signal transduction in melanoma have shown that both utilize STAT5 signaling to regulate apoptosis and cell proliferation, PI3K to modulate apoptosis, FAK to control migration, and the Ras/Raf/MEK/MAPK pathway to regulate cell survival, proliferation, and differentiation. Further, Xmrk and EGFR may also modulate similar chemokine, extracellular matrix, oxidative stress, and microRNA signaling pathways in melanoma. In hepatocellular carcinoma (HCC), Xmrk and EGFR signaling utilize STAT5 to regulate cell proliferation, and Xmrk may signal through PI3K and FasR to modulate apoptosis. At the same time, both activate the Ras/Raf/MEK/MAPK pathway to regulate cell proliferation and E-cadherin signaling. Xmrk models of melanoma have shown that inhibitors of PI3K and MEK have an anti-cancer effect, and in HCC, that the steroidal drug, adrenosterone, can prevent metastasis and recover E-cadherin expression, suggesting that fish Xmrk models can exploit similarities with EGFR signal transduction to identify and study new chemotherapeutic drugs.

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The epidermal growth factor receptor variant type III mutation frequently found in gliomas induces astrogenesis in human cerebral organoids

Cited by 13 publications

References 23 publications

A Genome-Wide Profiling of Glioma Patients with an IDH1 Mutation Using the Catalogue of Somatic Mutations in Cancer Database

A Genome-Wide Profiling of Glioma Patients with an IDH1 Mutation Using the Catalogue of Somatic Mutations in Cancer Database

Development of glioblastoma organoids and their applications in personalized therapy

Xmrks the Spot: Fish Models for Investigating Epidermal Growth Factor Receptor Signaling in Cancer Research

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