Navigation Links
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 of the tumor is conditioned around such mutations, so if you eliminate the oncogene, the tumor shrinks," Dr. Garraway said. Examples include the c-kit tyrosine kinase that drives development of gastrointestinal stromal tumors (GISTs), and certain EGFR mutations that are responsible for one form of lung cancer. These cancers can be treated with the targeted therapies Gleevec and Tarceva, respectively, which shut down the affected oncogenes.

The test involves taking a sample of fresh or frozen tumor, amplifying its DNA, and then searching for 250 known mutations in 17 oncogenes. (These include members of the ras, EGFR, pi3 and c-kit kinase families, among others.) To check performance of the genotyping, the research team tested over 1,000 tumors, representing 15 different cancer types, and then independently verified over half of the mutations they identified using traditional DNA sequencing or other methods. They found that over 92 percent of mutations identified by the mass spectrometry method were validated in this manner, and believe that much of the difference is due not to the mass spectrometry method but to limitations of the laborious sequencing test "which is not always sensitive in tumor specimens," Dr. Garraway said.

He added that the mass spectrometry test offers information that is distinct from the cancer microarray gene expression tests now being developed. "Those tests depend on gene expression while this one looks directly at problems in the genome," Dr. Garraway said.


'"/>

Source:American Association for Cancer Research


Related biology news :

1. Scientists tie several cancers to common oncogene engine
2. Pair of microRNA molecules controls major oncogene in most common leukemia
3. Novel technology detects human DNA mutations
4. Fox Chase Cancer Center scientists identify immune-system mutation
5. Mitochondrial DNA mutations play significant role in prostate cancer
6. Same mutation aided evolution in many fish species, Stanford study finds
7. Bioelectronic ‘signatures?hold key to DNA mutations
8. Sugar beet virus mutation requires Texas touch
9. Multi-species genome comparison sheds new light on evolutionary processes, cancer mutations
10. Treatments have same target, different responses for lung cancer patients with genetic mutation
11. Newly recognized gene mutation may reduce seeds, resurrect plants
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/1/2017)... 1, 2017  Aware, Inc. (NASDAQ: AWRE), a leading ... Richard P. Moberg has resigned, effective March 3, ... Financial Officer and Treasurer of Aware citing a desire ... a member of the Board of Directors of Aware. ... Executive Officer and co-President, General Counsel has been named ...
(Date:2/26/2017)... DALLAS , Feb. 25, 2017  Securus ... justice technology solutions for public safety, investigation, corrections ... of Recidivism and Reentry. "Too often, ... State prisons and county jails are trying to ... of inmates and friends and family members. While significant ...
(Date:2/16/2017)... , Feb. 16, 2017  Genos, a community ... that it has received Laboratory Accreditation from the ... is presented to laboratories that meet stringent requirements ... scientifically rigorous processes. "Genos is committed ... laboratory practices. We,re honored to be receiving CAP ...
Breaking Biology News(10 mins):
(Date:3/28/2017)... (PRWEB) , ... March 28, ... ... announced its partnership with the American Association for the Advancement of Science ... Science. Through this partnership, ReadCube will enhance its high-impact scholarly collection across ...
(Date:3/28/2017)... ... March 28, 2017 , ... Franz Inc ., the leading supplier of ... been named a ‘Champion’ by Bloor Research in its recent Graph Database Market ... class, and, thanks to Gruff, it was rated as the easiest product to use.” ...
(Date:3/28/2017)... ... March 28, 2017 , ... ... of the Modular Building Institute (MBI), an international modular trade organization, were awarded ... modular category for the Pagliuca Life Lab at Harvard University. The awards were ...
(Date:3/28/2017)... 28, 2017 Volition America, Inc., a wholly-owned U.S. ... engagement of Deborah Vollmer Dahlke , DrPH, CEO and ... Vollmer Dahlke,s role will be to assist the ... State of Texas and elsewhere in ... has significant experience over the past six years, helping ...
Breaking Biology Technology: