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High-throughput oncogene mutation detection in human cancers by mass spectrometry-based genotyping

Researchers have devised a new method to detect a spectrum of known gene mutations in a variety of cancer genes that they say is both sensitive and cost-effective. They say that if validated, this method of genotyping might ultimately be used in "real time" to match patients to available targeted therapies.

Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

The technique, developed at the Dana-Farber Cancer Institute and the Broad Institute of Harvard and MIT, may also offer aid in the testing and development of tailored treatments, according to researcher Levi A. Garraway, M.D., Ph.D., an assistant professor in the Dana-Farber Department of Medical Oncology. "It may help clinical testing of new targeted therapies, because patients can, in principle, be screened in advance for activating mutations in the protein the agent is directed against," he said.

It could also help eliminate a "significant bottleneck" in the development of drugs, which is the ability to test for multiple types of cancer genetic alterations simultaneously in the clinic. "Tests that use DNA sequencing to look for mutations in a single gene can cost a couple thousand dollars," Dr. Garraway said. "We ran a whole panel of genes for about $60 each, and the price could drop below that with more updated methods."

The method uses high-throughput mass spectrometry-based genotyping, which is a sensitive and accurate method to detect single nucleotide polymorphisms (SNPs) in DNA. But while this tool is mostly used to understand how single letter (or nucleotide) changes in genes might correlate with disease risk in normal individuals, the researchers adapted it to look for known point mutations in genes that make them oncogenic.

They chose oncogenes known to contain "dominant activating mutations in many tumor types. In a lot of cases, the entire biology
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Source:American Association for Cancer Research


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