Key Genetic Mutations in Brain Tumors Identified by Scientists from J. Craig Venter Institute, Ludwig Institute for Cancer Research, and The Johns Hopkins University School of Medicine
Sequencing of Receptor Tyrosine Kinases Reveals Three Novel Mutations
ROCKVILLE, MD — September 26, 2005 — Scientists from J. Craig Venter Institute, Ludwig Institute for Cancer Research, and The Johns Hopkins University School of Medicine identified three novel mutations in two receptor tyrosine kinases in glioblastoma tumors using high throughput sequencing. The mutations provide the potential for highly-targeted cancer therapies, as receptor tyrosine kinases can be targeted by either small molecules or antibodies. Results from the study will be published this week in the Proceedings of the National Academy of Sciences (PNAS). Researchers from the University of California, San Diego also contributed to the project.
Using high throughput DNA sequencing, researchers conducted the first comprehensive DNA sequence analysis of the receptor tyrosine kinase gene family in glioblastomas, an aggressive form of brain cancer. Recent studies have shown receptor tyrosine kinases to be cell regulators responsible for rapid cell growth in cancers, including colorectal, lymphoma, breast, and ovarian cancer.
"We have developed and applied high throughput DNA sequencing technologies and bioinformatics tools to peer into the genomes of glioblastomas in a manner that was previously unattainable," noted Robert L. Strausberg, Ph.D., deputy director of J. Craig Venter Institute and vice president of Human Genomic Medicine, J. Craig Venter Institute.
Researchers sequenced genes from 19 glioblastoma tumors from eight females and 11 males ranging in age from 7 to 77 years and analyzed them against healthy DNA samples. The bi-directional dideoxy sequencing of 20 receptor kinase domains and their adjacent regions revealed novel somatic mutations in fibroblast growth receptor 1 (FGFR1) and frameshift mutations in growth factor receptor alpha (PDFGRA).
"Having identified these previously unknown mutations in key cancer causing genes, we will hopefully enable the development of small molecules and antibodies to regulate their abnormal function and thus inhibit the growth of cancerous cells," explained Andrew Simpson, Ph.D., associate director-programs at Ludwig Institute for Cancer Research. "This collaborative study exemplifies exactly what our coalition was formed to do — leverage our individual institution's expertise to collectively discover new druggable targets through genome sequencing and functional genomic analysis."
About J. Craig Venter Institute
The J. Craig Venter Institute is a not-for-profit research institute dedicated to the advancement of the science of genomics; the understanding of its implications for society; and communication of those results to the scientific community, the public, and policymakers. Founded by J. Craig Venter, Ph.D., the Venter Institute is home to approximately 200 staff and scientists with expertise in human and evolutionary biology, genetics, bioinformatics/informatics, information technology, high-throughput DNA sequencing, genomic and environmental policy research, and public education in science and science policy. J. Craig Venter Institute is a 501(c)(3) organization. For additional information, please visit http://www.venterinstitute.org
About Ludwig Institute for Cancer Research
The Ludwig Institute for Cancer Research (LICR) is the largest international academic institute dedicated to understanding and controlling cancer. With nine Branches in seven countries, and numerous Affiliates and Clinical Trial Centers in many others, the scientific network that is LICR quite literally covers the globe. The uniqueness of LICR lies not only in its size and scale, but also in its philosophy and ability to drive its results from the laboratory into the clinic. LICR has developed an impressive portfolio of reagents, knowledge, expertise, and intellectual property, and has also assembled the personnel, facilities, and practices necessary to patent, clinically evaluate, license, and thus translate, the most promising aspects of its own laboratory research into cancer therapies.
J. Craig Venter Institute
Sarah L. White
Ludwig Institute for Cancer Research