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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Citation: Lee JC, Vivanco I, Beroukhim R, Huang JH, Feng WL, et al. (2006) Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain. PLoS Med 3(12): e485.
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