Sequence survey of receptor tyrosine kinases reveals mutations in glioblastomas

Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14344-9. doi: 10.1073/pnas.0507200102. Epub 2005 Sep 26.


It is now clear that tyrosine kinases represent attractive targets for therapeutic intervention in cancer. Recent advances in DNA sequencing technology now provide the opportunity to survey mutational changes in cancer in a high-throughput and comprehensive manner. Here we report on the sequence analysis of members of the receptor tyrosine kinase (RTK) gene family in the genomes of glioblastoma brain tumors. Previous studies have identified a number of molecular alterations in glioblastoma, including amplification of the RTK epidermal growth factor receptor. We have identified mutations in two other RTKs: (i) fibroblast growth receptor 1, including the first mutations in the kinase domain in this gene observed in any cancer, and (ii) a frameshift mutation in the platelet-derived growth factor receptor-alpha gene. Fibroblast growth receptor 1, platelet-derived growth factor receptor-alpha, and epidermal growth factor receptor are all potential entry points to the phosphatidylinositol 3-kinase and mitogen-activated protein kinase intracellular signaling pathways already known to be important for neoplasia. Our results demonstrate the utility of applying DNA sequencing technology to systematically assess the coding sequence of genes within cancer genomes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Brain Neoplasms / genetics*
  • Child
  • Evolution, Molecular*
  • Female
  • Genomics / methods
  • Glioblastoma / genetics*
  • Humans
  • Male
  • Models, Genetic
  • Models, Molecular*
  • Molecular Sequence Data
  • Mutation / genetics*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Sequence Analysis, DNA


  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Platelet-Derived Growth Factor alpha