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Giving DNA’s second code first priority
March 2006
by Jeffrey Bouley  |  Email the author


ST. LOUIS —Orion Genomics is aggressively working to decipher the "second code" of DNA to advance the state of cancer diagnostics and treatment, and has enlisted the help of researchers at the University of Glasgow to that end. The work currently focuses on discovering novel epigenetic biomarkers for the development of tests that screen for cancer at an early stage and that could provide personalized information about how tumors are most effectively treated.
Under the collaboration, scientists at Orion and the University of Glasgow will use Orion's methylation technologies to identify biomarkers useful in the detection and treatment of cancers of the lung, breast and ovaries. DNA methylation patterns, which Orion refers to as "second-code" biomarkers, provide information on the regulation of genes.
"Methylation is important to drug discovery, diagnostics and individualized cancer treatment because this second code silences promoter genes," notes Nathan Lakey, CEO of Orion Genomics. "A gene cannot be expressed if its promoter is methylated, so DNA methylation plays a fundamental role in determining the differential patient response and differential effectiveness of cancer drugs."
This fact is especially important in cancer treatment, he says, as he has not encountered or heard of a single example of a tumor that doesn't have genome-wide methylation changes.
"The literature has shown that changes in specific loci have a profound correlation to differential response to cancer therapies," Lakey adds. "So it's pretty clear to us that the specific methylation of pathways that are important for drug response are an important consideration in drug development and drug selection."
Working with the University of Glasgow 's Dr. Robert Brown is a boon to Orion's work, Lakey says.
"Professor Bob Brown is a leader in translation research who has dedicated much of his career to understanding the role of methylation in cancer," Lakey notes. "Professor Brown—working together with clinical trial groups, ethics committees and with support from Cancer Research UK—has carefully assembled tumor banks that will enable scientists in his lab, in collaboration with Orion, to find biomarkers for novel therapy selection and screening diagnostics and will expand Orion's exciting pipeline of diagnostic products."
Because Brown already had such a collection, having gathered it even before the technology existed to truly understand it, Orion can shave at least five years off its work in this area, Lakey says, saving a great deal of time, and therefore money.
"For us to collect samples now and follow outcomes would have take at least five years, and probably more like 10," he says.

The research will use Orion's proprietary DNA methylation technologies, including MethylScope microarrays and MethylScreen PCR assays. The groups will compare patterns of DNA methylation from normal and tumor DNA to identify specific patterns of abnormal methylation that indicate the presence of cancer and provide information about its stage and type. Orion will develop novel diagnostics based on these patterns that detect trace amounts of methylated tumor DNA in easily accessed patient samples including blood serum, biopsies, and cell scrapes.

"DNA methylation-based diagnostics have the potential to substantially change the way physicians first diagnose and later treat cancer patients," said Brown. "We are excited to collaborate with Orion Genomics, whose microarray and PCR technologies are at the world forefront for methylation analysis, both for marker discovery and for applying methylation diagnostics in a clinical setting. These types of technologies may prove to be extremely powerful if DNA methylation diagnostics are to be used to improve patient outcome and as part of novel strategies in clinical trials."

Code: E030618



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