Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain
2006

New Mutations in EGFR Linked to Glioblastoma

Sample size: 151 publication Evidence: moderate

Author Information

Author(s): Lee Jeffrey C, Vivanco Igor, Beroukhim Rameen, Huang Julie H. Y, Feng Whei L, DeBiasi Ralph M, Yoshimoto Koji, King Jennifer C, Nghiemphu Phioanh, Yuza Yuki, Xu Qing, Greulich Heidi, Thomas Roman K, Paez J. Guillermo, Peck Timothy C, Linhart David J, Glatt Karen A, Getz Gad, Onofrio Robert, Ziaugra Liuda, Levine Ross L, Gabriel Stacey, Kawaguchi Tomohiro, O'Neill Keith, Khan Haumith, Liau Linda M, Nelson Stanley F, Rao P. Nagesh, Mischel Paul, Pieper Russell O, Cloughesy Tim, Leahy Daniel J, Sellers William R, Sawyers Charles L, Meyerson Matthew, Mellinghoff Ingo K

Primary Institution: Dana-Farber Cancer Institute, Harvard Medical School

Hypothesis

Are there novel missense mutations in the extracellular domain of EGFR that contribute to glioblastoma?

Conclusion

The study identifies missense mutations in the extracellular domain of EGFR as a new mechanism for its activation in glioblastoma.

Supporting Evidence

  • Missense mutations were found in 14.4% of glioblastomas and 12.5% of glioblastoma cell lines.
  • These mutations were associated with increased EGFR gene dosage.
  • Cells with these mutations showed anchorage-independent growth and were sensitive to EGFR inhibitors.

Takeaway

Scientists found new changes in a protein called EGFR that can help brain tumors grow. This could help doctors find better treatments for patients.

Methodology

The researchers sequenced the entire EGFR coding region in 151 glioma tumors and cell lines to identify mutations.

Limitations

The study primarily involved patients of Northern European descent, which may limit the generalizability of the findings.

Participant Demographics

The study included 151 glioma samples, primarily glioblastomas, with a focus on patients of Northern European descent.

Digital Object Identifier (DOI)

10.1371/journal.pmed.0030485

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