Sequence survey of receptor tyrosine kinases reveals mutations in glioblastomas

Vikki Rand, Jiaqi Huang, Tim Stockwell, Steve Ferriera, Oleksandr Buzko, Samuel Levy, Dana Busam, Kelvin Li, Jennifer B. Edwards, Charles Eberhart, Kathleen M. Murphy, Alexia Tsiamouri, Karen Beeson, Andrew J.G. Simpson, J. Craig Venter, Gregory J. Riggins, Robert L. Strausberg

Research output: Contribution to journalReview articlepeer-review

Abstract

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-α gene. Fibroblast growth receptor 1, platelet-derived growth factor receptor-α, 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.

Original languageEnglish (US)
Pages (from-to)14344-14349
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number40
DOIs
StatePublished - Oct 4 2005

Keywords

  • Cancer
  • Fibroblast growth factor receptor 1
  • Genome
  • Platelet-derived growth factor receptor-α

ASJC Scopus subject areas

  • General

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