Sequence survey of receptor tyrosine kinases reveals mutations in glioblastomas.

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-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.

• Authors: 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
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 102 Issue 40 Pg. 14344-9 (Oct 04 2005) ISSN: 0027-8424 [Print] United States
• PMID: 16186508 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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