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Novel EGFR ectodomain mutations in glioblastoma

The Epidermal Growth Factor Receptor (EGFR), a so-called kinase protein, is often abnormally active in cancer. A new class of anticancer drugs inhibiting the activated EGFR kinase have shown to be effective against such cancers, especially lung cancer. In a new study in PLoS Medicine, researchers have catalogued and characterized the mutations in the EGFR gene that occur in glioblastoma, a deadly type of brain tumor. The researchers sequenced the whole coding sequence of the EGFR gene in more than 100 glioblastomas. Nearly 15% of the tumors contained missense mutations—changes that altered the amino acid sequence of EGFR.

But the mutations were mostly different from the ones commonly seen in other cancers: rather than changing the kinase domain, most of the gliobastoma-associated mutations mapped to the extracellular domain of the protein. These findings identify missense mutations in the extracellular domain of EGFR as a new way to oncogenically activate this protein. Fortunately, the drugs developed to inhibit EGFR have broad activity, which bodes well for the use of these drugs in patients with glioblastoma.
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Source:Public Library of Science


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