Orion Genomics (St. Louis) last week reported the discovery of new breast cancer biomarkers that it says may someday lead to earlier detection – and possibly better treatment – of the disease.

The company said it has discovered and validated what it believes to be the most frequent DNA alterations detected in breast cancer to date.

The results of a genome-wide analysis of DNA methylation were published in PLoS ONE. The study, “Identification of Novel High-Frequency DNA Methylation Changes in Breast Cancer” found more than 50 biomarkers, which were subsequently validated in up to 230 independent patient samples, according to Orion.

“Our study identified novel biomarkers that were individually capable of distinguishing early stage ductal breast cancer from normal and benign breast tissue,” said Jared Ordway, PhD, director of R&D at Orion. “We are very excited about the potential of these findings as these biomarkers may be critical in the development of molecular diagnostics for the early detection of breast cancer.”

Ordway told Medical Device Daily that in addition to early-stage detection of breast cancer, other applications the company plans to explore with the biomarkers include prognostic applications, the detection of risk and reoccurrence of the disease.

“We’re interested in looking at the association between having these particular biomarkers and responses to specific therapies. So those applications would be ones where a primary tissue itself would be analyzed for the marker or a combination of markers ... used to determine what the likely prognoses would be,” Ordway said.

In the study, researchers applied a microarray-based approach to map tumor-associated changes in DNA methylation, alterations that can affect normal gene expression.

Nathan Lakey, president/CEO of Orion, told MDD that a single locus associated with the GHSR gene was the most powerful biomarker in the study, with a clinical sensitivity of 90% and a specificity of 96% for infiltrating ductal breast carcinoma.

In addition to identifying biomarkers that might aid in the detection of breast cancer, the research revealed insights into the molecular mechanism of tumor development, which may lead to advances in breast cancer treatment, Orion noted.

Lakey said the company is now validating these markers to see if they are useful for predicting risk, to determine if they can be found in body fluids, to find out if they are able to predict prognosis or therapy response, and to determine to what extent these markers are implicated in other cancer types.

“Twelve of our more than 50 breast cancer biomarkers exceeded the highest sensitivity previously reported for the stratification of tumor and normal tissue,” Lakey said. “These results validate our biomarker discovery platform and our product pipeline, which is focused on breast, lung and ovarian cancer diagnostics.”

According to Orion, its MethylScope technology enables genome-wide DNA methylation profiling.

MethylScope is a best-in-class DNA analysis tool compatible with microarray, bead array and ultra high-throughput DNA sequencing technologies, the company said. Using MethylScope technology, Orion says its scientists and partners are able to simultaneously study the epigenetic state of every human gene as well as tens of thousands of other loci to discover DNA methylation biomarkers important in epigenetic disorders like cancer.

Orion has also developed a MethylScreen technology to “meet the need for a clinical assay system to detect and quantify trace amounts of DNA methylation-based biomarkers in clinical samples.” MethylScreen technology precisely identifies these biomarkers using a process that relies on restriction digestion and quantitative PCR, robust procedures routinely practiced in high-volume reference laboratories worldwide, Lakey told MDD.

MethylScreen assays are capable of detecting trace amounts of tumor signal through the use of a combination of restriction enzymes selected to destroy normal copies of a locus, leaving intact disease-associated copies that are amplified and detected by quantitative PCR, according to Orion. A MethylScreen assay determines the concentration of a disease biomarker and quantifies the methylation density of the biomarker in a sample.

Orion develops genomic research tools and molecular diagnostic products to detect cancer at its earliest stages and to aid in appropriate therapy selection. The company says that it has active biomarker discovery programs in cancers of the bladder, breast, lung, ovaries and colon.

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