Clinical OMICS

JAN-FEB 2019

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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22 Clinical OMICs January/February 2019 www.clinicalomics.com 2015 in Clinical Epigenetics and have been working since to develop the assay, following patients to make the necessary correlations of the DNA methylation markers to recurrence. Some of the most prom- ising translational research involving epigenetic mark- ers is being done in the area of cancer diagnosis and prognosis. In May 2018, Delphine Lissa, Pharm. D. and Ph.D., and her colleagues published the results of a retrospective study in Lung Cancer. The study validated an assay that quantified methylation of a gene that codes for a DNA-binding transcription factor, called Homeobox A9 (HOXA9), which previous stud- ies had identified as being associated with lung cancer. The current study goes a step further. "We showed that the methylation of HOXA9 is associated with higher risk in patients with early stage lung cancer," said Lissa, a post-doc- toral fellow at the National Cancer Institute. Researchers used digital droplet PCR (ddPCR) to quantify methylation of the HOXA9 gene in tumor samples. The technology uses oil droplets to divide the PCR solution into 20,000 smaller reactions, enabling more precise, digital quantification than standard PCR and making the technique highly sensitive. The resulting mea- surements of methylation in the current study, both alone and in combination with blood vessel inva- sion assessment (a negative predictor of sur- vival), allowed researchers to stratify stage I patients with lung adenocarcinoma. "High methylation was associated with poor prognosis," the authors wrote. These findings are important, Lissa said, because, currently, patients with lung adenocarcinoma at the same stage, experience different outcomes after sur- gery, the only curative option for these patients. Unfortunately, about one-third of the patients develop recurrence and die within five years, Lissa said. This methylation biomarker could help optimize therapy decisions for patients at high-risk for recurrence" Lissa said. Eventually, the goal is to find more such epigenetic or other biomarkers that could be included in a prognos- tic or diagnostic panel for patients with lung adenocarci- noma, Lissa said. For now, she and her collaborators will be working to validate the current assay and biomarker in a larger cohort of patients. They plan to do this in a prospec- tive cohort, reproducing the current results. Future plans include using the assay on urine and in conjunction with liquid biopsy, retrieving tumor cells instead of using tumor tissue collected via standard biopsy. Cardiovascular Disease Markers Cardiovascular disease research is also currently focused on prognosis and identifying epigenetic markers that could be used in calculating risk of heart attacks in patients. That's because, right now, only 60% to 80% of risk can be ascribed to genetics or lifestyle. "When you are talking about some- thing that might kill you, you want much better certainty than that. On the risk-prediction side, we are using epi- genetics," said Svati Shah, M.D., associate professor of med- icine and co-director of translational research within the Duke University's Molecular Physiology Insti- tute. In a November 2015 paper pub- lished in PLOS Genetics, a group led by Shah found endo- plasmic reticulum (ER) stress to be associ at ed w i t h (continued from previous page) Delphine Lissa, Pharm. D. and Ph.D., National Cancer Institute "When you are talking about something that might kill you, you want much better certainty than that. On the risk-prediction side, we are using epigenetics." —Svati Shah, M.D., Molecular Physiology Institute, Duke University Tomekbudujedomek / Moment / Getty Images

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