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General Information
Name
cancer, malignant glioma, EGFR-MYC-related
FlyBase ID
FBhh0000403
Disease Ontology Term
Parent Disease
OMIM
Overview

This Drosophila model of malignant glioma uses the GAL4/UAS system to drive overexpression of Dmel\Egfr and Dmel\Myc in glial cells and glial precursors. Epidermal growth factor receptor (EGFR) has been implicated in multiple cancers (see FBhh0000398); more than 40% of glioblastomas show amplification and/or mutation of EGFR. Mutations, overexpression, and rearrangements of MYC oncogene have also been implicated in multiple cancers (see FBhh0000402).

EGFR overexpression has been achieved by using a Dmel\Egfr fusion gene that contains a λ dimerization domain; this results in a constitutively active Egfr via forced dimerization. Overexpression of Dmel\Myc has been achieved using a wild-type transgenic copy of the gene; co-overexpression with the Egfr fusion gene induces glial neoplasia in third instar larval brains. This model system has been used to screen for genes that interact genetically to suppress or enhance the glial neoplastic phenotype; see the "Alleles Reported to Model Human Disease" section, below.

[updated Oct. 2016 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, malignant glioma, EGFR-MYC-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology

Glioblastoma multiforme and other malignant gliomas are characterized by a heterogeneous population of cells that are highly infiltrative, angiogenic and resistant to chemotherapy (Ramirez et al., 2013; pubmed:24287492).

Glioblastoma multiforme is a malignant astrocytoma and the most common primary brain tumor among adults (reviewed in Furnari et al., 2007; pubmed:17974913).

Molecular information

MYC encodes a transcription factor that plays a role in cell cycle progression, apoptosis and cellular transformation. [from Gene Cards, MYC; 2016.09.30]

External links
Disease synonyms
glioblastoma
glioma
cancer, glioblastoma, EGFR-MYC-related
cancer, neuronal, EGFR-MYC-related
brain cancer, EGFR-MYC-related
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one (3 human to 1 Drosophila); additional (lower-scoring) human orthologs are MYCN and MYCL.

    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one (4 human to 1 Drosophila); additional human orthologs are ERBB4, ERBB3, and ERBB2.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (3)
      Gene Snapshot
      Epidermal growth factor receptor (Egfr) encodes the transmembrane tyrosine kinase receptor for signaling ligands (encoded by grk, spi, vn, and Krn) in the TGFα family, which utilises the intracellular MAP kinase pathway. The product of Egfr contributes to growth regulation, cell survival and developmental patterning. [Date last reviewed: 2019-06-06]
      Gene Groups / Pathways
      Comments on ortholog(s)

      Orthologous to human genes EGFR, ERBB4, ERBB3, and ERBB2 (1 Drosophila to 4 human). Dmel\Egfr shares 33-37% identity and 46-51% similarity with the human genes.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Gene Snapshot
      Myc (Myc) encodes a transcription factor that is homologous to vertebrate Myc proto-oncogenes. It contributes to cell growth, cell competition and regenerative proliferation. [Date last reviewed: 2019-03-14]
      Gene Groups / Pathways
      Comments on ortholog(s)

      Orthologous to human gene MYC (reciprocal best hit); lower scoring ortholog of human MYCN and MYCL (1 Drosophila to 3 human). Dmel\Myc shares 31% identity and 44% similarity with human MYC, within the carboxy extents of the two proteins; the amino extents do not align.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Molecular function (GO)
        Cellular component (GO)
          Gene Groups / Pathways
            Comments on ortholog(s)

            Constructs with this fusion gene plus a λ dimerization domain and a UAS promoter produce a constitutively active Egfr via forced dimerization; expression controlled by use of different GAL4 drivers.

            Orthologs and Alignments from DRSC
            DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
            Synthetic Gene(s) Used (0)
            Summary of Physical Interactions (124 groups)
            RNA-protein
            Interacting group
            Assay
            References
            rna three hybrid
            protein-protein
            Interacting group
            Assay
            References
            anti tag coimmunoprecipitation, anti tag western blot, solid phase assay, tag visualisation by fluorescence
            anti bait coimmunoprecipitation, western blot
            anti bait coimmunoprecipitation, western blot
            anti tag coimmunoprecipitation, peptide massfingerprinting
            anti tag coimmunoprecipitation, western blot, pull down, anti tag western blot
            anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
            anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, peptide massfingerprinting, pull down, two hybrid
            anti tag coimmunoprecipitation, western blot, pull down, anti tag western blot
            anti tag coimmunoprecipitation, peptide massfingerprinting
            anti tag coimmunoprecipitation, western blot, enzyme linked immunosorbent assay, anti tag western blot
            anti tag coimmunoprecipitation, peptide massfingerprinting
            anti tag coimmunoprecipitation, peptide massfingerprinting
            anti tag coimmunoprecipitation, peptide massfingerprinting
            anti tag coimmunoprecipitation, anti tag western blot
            anti tag coimmunoprecipitation, peptide massfingerprinting
            anti tag coimmunoprecipitation, peptide massfingerprinting
            anti tag coimmunoprecipitation, anti tag western blot, pull down, western blot
            anti tag coimmunoprecipitation, anti tag western blot, pull down, western blot
            pull down, western blot, anti tag coimmunoprecipitation, anti tag western blot, two hybrid, anti bait coimmunoprecipitation
            anti bait coimmunoprecipitation, western blot
            surface plasmon resonance, solid phase assay, tag visualisation by fluorescence, x-ray crystallography
            anti tag coimmunoprecipitation, peptide massfingerprinting
            anti tag coimmunoprecipitation, anti tag western blot, two hybrid
            two hybrid, anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, peptide massfingerprinting
            protein-protein
            Interacting group
            Assay
            References
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti bait coimmunoprecipitation, anti tag western blot, anti tag coimmunoprecipitation, western blot, two hybrid, tandem affinity purification, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti bait coimmunoprecipitation, western blot
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, anti tag western blot
            pull down, autoradiography, anti bait coimmunoprecipitation, anti tag western blot, proximity ligation assay, fluorescence microscopy, anti tag coimmunoprecipitation, western blot
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            pull down, autoradiography, anti tag coimmunoprecipitation, anti tag western blot
            anti bait coimmunoprecipitation, western blot
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, anti tag western blot
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti bait coimmunoprecipitation, western blot, pull down, autoradiography, anti tag western blot
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            pull down, autoradiography, anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, western blot
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti bait coimmunoprecipitation, western blot, pull down, autoradiography
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            pull down, autoradiography, anti tag coimmunoprecipitation, anti tag western blot, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti bait coimmunoprecipitation, western blot
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, anti tag western blot
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, western blot
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            anti tag coimmunoprecipitation, Identification by mass spectrometry
            RNA-protein
            Interacting group
            Assay
            References
            anti bait coimmunoprecipitation, quantitative reverse transcription pcr
            anti tag coimmunoprecipitation, primer specific pcr
            RNA-RNA
            Interacting group
            Assay
            References
            western blot, quantitative reverse transcription pcr
            Alleles Reported to Model Human Disease (Disease Ontology) (0 alleles)
            Genetic Tools, Stocks and Reagents
            Sources of Stocks
            Contact lab of origin for a reagent not available from a public stock center.
            Bloomington Stock Center Disease Page
            Selected mammalian transgenes
            Allele
            Transgene
            Publicly Available Stocks
            Selected Drosophila transgenes
            Allele
            Transgene
            Publicly Available Stocks
            RNAi constructs available
            Allele
            Transgene
            Publicly Available Stocks
            Selected Drosophila classical alleles
            Allele
            Allele class
            Mutagen
            Publicly Available Stocks
            loss of function allele
            ethyl methanesulfonate
            loss of function allele
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            gamma ray
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            loss of function allele
            ethyl methanesulfonate
            loss of function allele
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            loss of function allele
            ethyl methanesulfonate
            loss of function allele
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            gamma ray
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            amorphic allele - genetic evidence
            gamma ray
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            amorphic allele - molecular evidence
            P-element activity
            References (7)