Clinical OMICS

MAR-APR 2017

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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Page 36 of 47 March/April 2017 Clinical OMICs 35 racy by multiple clinical laboratories, laying the groundwork for future clin- ical utility . The results clearly show that locked and controlled procedures permit the reliable, accurate, and reproducible use of NGS for clinical purposes . The NCI-MATCH investigators, using the Oncomine Cancer Panel assay and the Personal Genome Machine, were able to detect more than 4,000 predefined genomic vari- ations across 143 genes, including single nucleotide variants (SNVs), insertions/deletions (indels), copy number variations (CNVs), and gene fusions . "We report the analytical validation processes for the NGS assay that was tailored for regulatory compliant use in the trial," the authors wrote. "The Oncomine Cancer Panel assay and the Personal Genome Machine were used in four networked laboratories accredited for the Clinical Laboratory Improvement Amendments (CLIA) . Using formalin-fixed, paraffin-embed- ded clinical specimens and cell lines, we found that the assay achieved an overall sensitivity of 96 . 98% for 265 known mutations and 99.99% specific- ity . High reproducibility in detecting all reportable variants was observed, with a 99 . 99% mean interoperator pairwise concordance across the four laboratories." 186 samples and 12 cell lines were tested at four different labo- ratories . Steps were taken to maxi- mize standardization, including the development of standard operating procedures, use of the same com- mercial assay and instruments, and face-to-face discussions . The inves- tigators found that the assay results were highly reproducible, with the same results across multiple labora- tories . This is critical for future clin- ical use leading to improved patient outcomes . "This analytical validation study clearly found that the assay met the expected performance requirement for the intended use," the authors penned. "This validation effort indi- cates that NGS assays can be robust and reproducible if the assay sys- tem is defined and standardized by locked SOPs . The process described in this article can serve as a template for other investigators who develop and validate NGS assay systems." Most importantly, the authors noted that NCI-MATCH NGS assay was able to accurately determine genetic abnormalities in biopsies from the pancreas, melanoma, bone, and skin samples, which "suggests that nucleic acid specimens recovered from multi- ple tumor tissue types are acceptable." "The validation study reported by Williams and colleagues is another step moving the field closer to the time when precision medicine will generate the expected benefits in improved clinical outcomes," con- cluded Elizabeth Unger, M . D . , Ph . D . , chief of the Chronic Viral Disease Branch (CVDB), of the Division of High-Consequence Pathogens and Pathology at the Centers for Disease Control and Prevention . "Although the success of the NCI-MATCH trial cannot be assured, linking preci- sion laboratories to precision med- icine trials assures that data used for drug assignment will be reliable . Further, the use of a commercial platform and integrated analysis and reporting pipeline will greatly facilitate the broader translation of any successes." German Researchers Link Hereditary Factors of CAD with Other Diseases A new study published in the Journal of the American College of Cardiology by researchers from the German Cen- tre for Cardiovascular Research (DZHK) has identified six variants in the human genome that occur more frequently in coronary artery disease (CAD) and dis- covered that half of all 62 hereditary risk factors for CAD are also associated with entirely different diseases, such as schizophrenia, chronic inflammatory bowel disease, or migraines. In the published research, the Ger- man team performed a genome-wide association study (GWAS) comparing the genetic sequences from 42,335 people with coronary artery disease and 78,240 healthy people against 5,000 commonly occurring SNPs—many of which are already associated with other diseases. Subsequently, the researchers wanted to examine the phenomenon that hereditary risk factors are associated with different diseases more closely— which they did in the most comprehen- sive analysis of this kind to date for the known 62 CAD risk factors. A third of the 62 SNPs were associated with traditional risk factors for CADs, for instance, high blood pressure or cholesterol values. While these results were not surprising, nearly half of the SNPs also play a part in completely different diseases, such as schizophrenia or migraines. Nongkran_ch / Getty Images

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