Genetic Engineering & Biotechnology News

MAY15 2017

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8 | MAY 15, 2017 | | Genetic Engineering & Biotechnology News Biomarker Validation for Genomic Assays and Validation, a conference that recently took place in San Francisco. This event, which was organized by Cambridge Healthtech Institute (CHI), provided an opportunity for bio- specimen experts and assay developers to discuss the "major challenges and latest advances in sample preparation and the validation of NGS and other advanced diagnostics assays." Outstanding presentations from the CHI conference are summarized in this article. Like the conference, the main body of this article will start with observations offered by Lin Wu, Ph.D., vice president of development, Roche Se- quencing Solutions. Dr. Wu chose to emphasize best practices and approaches that could bring highly sensitive and robust assays to market. In particular, Dr. Wu cited guidelines that appeared in The Journal of Molecular Diagnostics. On March 16, a workgroup convened by the Centers for Disease Control and Prevention published a set of guidelines on molecular diagnostics ("Principles and Recommendations for Standardizing the Use of the Next-Generation Sequenc- ing Variant File in Clinical Settings"). Less than a week later, on March 21, the Association for Molecular Pathology and the College of American Pathologists issued an oncology- oriented joint consensus recommendation ("Guidelines for Validation of Next-Generation Sequencing-Based Oncology Panels"). Such efforts, Dr. Wu stated, "provide recommendations for validating genomic assays analytically and clinically." Moreover, they recognize that precious patient samples are critical for advancing genomic medicine. The importance of patient samples was also taken up by Benoit Bouche, Pharm.D., Ph.D., managing director, Trans- Hit Biomarkers. "Hundreds of R&D projects are stuck in labs because pharma companies behind projects cannot find the biospecimens needed for analytical and clinical valida- tion of assays," he lamented. The problem of limited tissue, commented Ping Qiu, Ph.D., principal scientist, Merck & Co., is especially trouble- some in oncology applications, which also contend with tu- mor heterogeneity and sequencing artifacts. "Oncology ap- plications of sequencing technologies are still in their infancy, especially in the immuno-oncology space," noted Dr. Qiu, who also complained of a lack of consistency in laboratory practices. "There is currently no industry standard," he said, "in terms of reference materials, DNA/RNA extraction, sam- ple input amounts, or bioinformatics pipelines, etc." The strategies pursued by different laboratories depend not only on the markers—whether DNA, RNA, or protein— but also on the types of questions that are being asked, and the technologies that are being used. Suppose a biomarker assay identifies a clinically actionable somatic mutation in a cancer. Is the mutation in 100 cells or 100% of the cells, or 10% or 5%? "You must pinpoint and validate," asserted Madhuri Hegde, Ph.D., adjunct professor, Emory University, and vice president and chief scientific officer, global laboratory servic- es, diagnostics, PerkinElmer. "This knowledge will drive the drug treatment for that patient." Although the challenges addressed at the CHI conference remain daunting, several presenters highlighted advances in biospecimen science, including promising results with un- conventional specimens. For example, David T.W. Wong, endowed professor, associate dean of research, UCLA School of Dentistry, discussed how saliva and salivaomics could be used in the detection of oncogenic mutations in human cancers. "Biomarker validation," insisted Wong, "is the key element in biomarker research, particularly in pa- tient research." "Real" Specimens in Potential Assays Dr. Wu verifies analytical performance of next-generation biomarker assays. "We are developing targeted biomarker panels to measure tumor-specific mutations in liquid biop- sies," she said, adding that Roche is also working on a panel to measure how many tumor mutations are in the patient's blood overall. Analytical validation technologies are considered prom- ising if they excel in terms of sensitivity, specificity, and re- producibility. Although performance attributes such as these are important, they do not, by themselves, guarantee success. Dr. Wu emphasized that analytical verification doesn't prove assays have clinical utility; the biomarkers therein may not be 100% proven for clinical use yet. Analytical studies must be done prior to moving assays to clinical validation; other- wise, resources and time could be wasted on precious patient samples and trials. "It is very important for us to complete the analytical biomarker studies before we commercialize the biomarker assays," confirmed Dr. Wu. Roche uses "real" clinical specimens and follows guide- line recommendations such as the ones recently published in Drug Discovery Feature Continued from page 1 A liquid biopsy technology is being developed by UCLA scientists to detect tumor-causing mutations in saliva and other bodily fluids. The technology, called electric field-induced release and measurement (EFIRM), leverages highly specific molecular probes and an enzymatic amplification system to achieve high-sensitivity detection of circulating tumor DNA and proteins associated with cancer. The EFIRM detection process takes place on a high-throughput electrode array, allowing for the testing of multiple patients and multiple cancer markers simultaneously.

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