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General Information
Name
cancer, malignant glioma, EGFR-related
FlyBase ID
FBhh0000399
Disease Ontology Term
Parent Disease
OMIM
Overview

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. The gene encodes a transmembrane receptor kinase that spans the cell membrane and is activated by a number of external ligands, including EGF and transforming growth factor α. Activation of EGFR initiates several signal transduction cascades, leading to DNA synthesis and cell proliferation. There is one orthologous gene in flies, Dmel\Egfr, for which classical amorphic and hypomorphic alleles, constitutively active alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\Egfr is orthologous to three additional human genes, ERBB4, ERBB3 and ERBB2. ERBBS has also been implicated in multiple cancers, including glioma susceptibility 1 (OMIM:137800).

The human gene Hsap\EGFR has been introduced into flies, using a mutant form that displays constitutive kinase activity and can be expressed in specific tissues using the GAL4-UAS system. Using a GAL4 construct that drives expression in glial cells, glial overgrowth, brain enlargement and lethality at third instar larval stage are observed; this genotype recapitulates some aspects of glioma. Overexpressing, in addition, a transgenic copy of Dmel\Pi3K92E results in a more robust model of malignant glioma in Drosophila (see FBhh0000401).

[updated Oct. 2016 by FlyBase; FBrf0222196]

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

More than 40% of glioblastomas (GBMs) show EGFR gene amplification, and these amplification events are often accompanied by mutations in EGFR; the most prevalent mutant form of EGFR is an intragenic truncation mutant that displays constitutive kinase activity (reviewed in Furnari et al., 2007; pubmed:17974913).

Cellular phenotype and pathology
Molecular information

Epidermal Growth Factor Receptor (EGFR) is a transmembrane receptor tyrosine kinase of the ErbB family. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Binding of DGFR can activate at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. [from Gene Cards, EGFR; 2016.09.30]

External links
Disease synonyms
glioblastoma
glioma
cancer, glioblastoma, EGFR-related
Search term: hyperplastic phenotype(s)
cancer, neuronal, EGFR-related
brain cancer, EGFR-related
Ortholog Information
Human gene(s) in FlyBase
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 (1)
    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
    Synthetic Gene(s) Used (0)
    Summary of Physical Interactions (33 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
    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
    References (6)