Multilaboratory Assessment of a New Reference Material for Quality Assurance of Cell-Free Tumor DNA Measurements
Publication date: Available online 2 May 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Hua-Jun He, Erica V. Stein, Yves Konigshofer, Thomas Forbes, Farol L. Tomson, Russell Garlick, Emiko Yamada, Tony Godfrey, Toshiya Abe, Koji Tamura, Michael Borges, Michael Goggins, Sandra Elmore, Margaret L. Gulley, Jessica L. Larson, Lando Ringel, Brian C. Haynes, Chris Karlovich, P. Mickey Williams, Aaron GarnettWe conducted a multilaboratory assessment to determine the suitability of a new commercially available reference material with 40 cancer variants in a background of wild-type DNA at four different variant allele f...
Source: The Journal of Molecular Diagnostics - May 24, 2019 Category: Pathology Source Type: research

Fixation Effects on Variant Calling in a Clinical Resequencing Panel
Publication date: Available online 2 May 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Jeremy D.K. Parker, Shyong Q. Yap, Elizabeth Starks, Jillian Slind, Lucas Swanson, T. Roderick Docking, Megan Fuller, Chen Zhou, Blair Walker, Douglas Filipenko, Wei Xiong, Ahmer A. Karimuddin, P. Terry Phang, Manoj Raval, Carl J. Brown, Aly KarsanFormalin fixation is the standard method for the preservation of tissue for diagnostic purposes, including pathologic review and molecular assays. However, this method is known to cause artifacts that can affect the accuracy of molecular genetic test results. We assessed the applic...
Source: The Journal of Molecular Diagnostics - May 24, 2019 Category: Pathology Source Type: research

Validation of Extensive Next-Generation Sequencing Method for Monogenic Disorder Analysis on Cell-Free Fetal DNA: Noninvasive Prenatal Diagnosis
We present a method for the analysis of an extended group of gene variants associated with recessive and dominant autosomal disorders using next-generation sequencing. The proposed test should allow a complete analysis of common genetic disorders and pathogen-associated variants for diagnostic use. The analysis of cffDNA for single gene disorders may replace invasive prenatal diagnosis methods, associated with the risk of spontaneous abortion and psychological stress for patients. The proposed test should assess reproductive risk for both genetic family disorders and de novo occurrences of the disease. The application of t...
Source: The Journal of Molecular Diagnostics - May 19, 2019 Category: Pathology Source Type: research

Detection of tumor NTRK gene fusions to identify patients who may benefit from TRK inhibitor therapy
Publication date: Available online 7 May 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Susan J. Hsiao, Ahmet Zehir, Anthony N. Sireci, Dara L. AisnerAbstractChromosomal rearrangements involving the NTRK1, NTRK2, and NTRK3 genes (NTRK gene fusions), which encode the TRKA, TRKB, and TRKC receptor tyrosine kinases, act as oncogenic drivers in a broad range of pediatric and adult tumor types. NTRK gene fusions have been shown to be actionable genomic events that are predictive of response to TRK kinase inhibitors, making their routine detection an evolving clinical priority. In certain exceedingly rare tumor types...
Source: The Journal of Molecular Diagnostics - May 8, 2019 Category: Pathology Source Type: research

Recommendations for Clinical CYP2C9 Genotyping Allele Selection: A Joint Recommendation of the Association for Molecular Pathology and College of American Pathologists
Publication date: Available online 8 May 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Victoria M. Pratt, Larisa H. Cavallari, Andria L. Del Tredici, Houda Hachad, Yuan Ji, Ann M. Moyer, Stuart A. Scott, Michelle Whirl-Carrillo, Karen E. WeckABSTRACTThe goals of the Association for Molecular Pathology Pharmacogenomics (PGx) Working Group of the Association for Molecular Pathology Clinical Practice Committee are to define the key attributes of PGx alleles recommended for clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This document provides recommendatio...
Source: The Journal of Molecular Diagnostics - May 8, 2019 Category: Pathology Source Type: research

Diagnostics Reform and Harmonization of Clinical Laboratory Testing
Publication date: Available online 8 May 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Jeff Schreier, Robert Feeney, Peter KeelingAbstractDevelopments in diagnostics reform legislation in the United States are occurring at a rapid pace. The framework for future regulatory oversight of clinical laboratory testing is currently under intensive debate among stakeholders that represent patients, providers, laboratories, diagnostic manufacturers, and regulators. The importance of clinical laboratory test standardization is a key component of any plan for regulatory reform. A laboratory-developed test is performed in...
Source: The Journal of Molecular Diagnostics - May 8, 2019 Category: Pathology Source Type: research

Multi-Laboratory Assessment of a New Reference Material for Quality Assurance of Cell-Free Tumor DNA Measurements
Publication date: Available online 2 May 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Hua-Jun He, Erica V. Stein, Yves Konigshofer, Thomas Forbes, Farol L. Tomson, Russell Garlick, Emiko Yamada, Tony Godfrey, Toshiya Abe, Koji Tamura, Michael Borges, Michael Goggins, Sandra Elmore, Margaret L. Gulley, Jessica L. Larson, Lando Ringel, Brian C. Haynes, Chris Karlovich, P. Mickey Williams, Aaron GarnettAbstractWe conducted a multi-laboratory assessment to determine the suitability of a new commercially-available reference material with 40 cancer variants in a background of wild type DNA at four different variant...
Source: The Journal of Molecular Diagnostics - May 3, 2019 Category: Pathology Source Type: research

Promoter hypermethylation of genes encoding for RASSF/Hippo pathway members reveals specific alteration pattern in diffuse gliomas
Publication date: Available online 2 May 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Guénaëlle Levallet, Christian Creveuil, Lien Bekaert, Elodie Péres, Gaëtane Planchard, Sylvie Lecot-Cotigny, Jean-Sébastien Guillamo, Evelyne Emery, Gérard Zalcman, Emmanuèle Lechapt-ZalcmanRASSF/Hippo pathway alterations are poorly characterized in diffuse gliomas. We assayed promoter methylation of LATS1/2, MST1(STK4)/MST2(STK3), RASSF1, RASSF2, Nore1A/RASSF5, RASSF6, and RASSF10 genes in 133 diffuse Grade II-III-IV gliomas, using methylation-specific PCR or PCR coupled to Cobra...
Source: The Journal of Molecular Diagnostics - May 3, 2019 Category: Pathology Source Type: research

Fixation Effects on Variant-Calling in a Clinical Resequencing Panel
Publication date: Available online 2 May 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Jeremy D.K. Parker, Shyong Quin Yap, Elizabeth Starks, Jillian Slind, Lucas Swanson, T. Roderick Docking, Megan Fuller, Chen Zhou, Blair Walker, Douglas Filipenko, Wei Xiong, Ahmer A. Karimuddin, P. Terry Phang, Manoj Raval, Carl J. Brown, Aly KarsanFormalin fixation is the standard method for preservation of tissue for diagnostic purposes, including pathological review and molecular assays. However, this method is known to cause artifacts that can affect the accuracy of molecular genetic tests. We assessed the applicability...
Source: The Journal of Molecular Diagnostics - May 3, 2019 Category: Pathology Source Type: research

Abstracts of the 2nd Global Congress on Molecular Pathology
Publication date: May 2019Source: The Journal of Molecular Diagnostics, Volume 21, Issue 3, SupplementAuthor(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - April 26, 2019 Category: Pathology Source Type: research

Author Index
Publication date: May 2019Source: The Journal of Molecular Diagnostics, Volume 21, Issue 3, SupplementAuthor(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - April 26, 2019 Category: Pathology Source Type: research

Development of a Novel Next-Generation Sequencing Assay for Carrier Screening in Old Order Amish and Mennonite Populations of Pennsylvania
Publication date: Available online 25 April 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Erin L. Crowgey, Michael C. Washburn, E. Anders Kolb, Erik G. PuffenbergerGenetically isolated populations such as the Old Order Amish and Old Order Mennonite communities have an increased incidence of specific autosomal recessive disorders due to the founder effect. In these populations, robust expanded carrier screening and diagnostic testing have the potential to reduce overall medical costs and improve patient outcomes. A novel next-generation sequencing assay was developed using anchored multiplex PCR technology (Arc...
Source: The Journal of Molecular Diagnostics - April 25, 2019 Category: Pathology Source Type: research

Validation of Extensive Next-Generation Sequencing Method for Monogenic Disorder Analysis on Cell Free Fetal DNA: Noninvasive Prenatal Diagnosis
We present a method for the analysis of an extended group of gene variants associated with recessive and dominant autosomal disorders using next-generation sequencing. The proposed test should allow a complete analysis of common genetic disorders and pathogen-associated variants for diagnostic use. The analysis of cffDNA for single gene disorders may replace invasive prenatal diagnosis methods, associated with the risk of spontaneous abortion and psychological stress for patients. The proposed test should assess reproductive risk both for genetic family disorders and de novo occurrences of the disease. The application of t...
Source: The Journal of Molecular Diagnostics - April 25, 2019 Category: Pathology Source Type: research

Adopting High-Resolution Allele Frequencies Substantially Expedites Variant Interpretation in Genetic Diagnostic Laboratories
Publication date: Available online 25 April 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Mahdi Ghani, Landry Nfonsam, Erinija Pranckeviciene, Hussein Daoud, Ryan Potter, Caitlin Chisholm, Patricia E. Harper, Audrey Schaffer, Leichelle Little, Elizabeth Sinclair-Bourque, Jean McGowan-Jordan, Amanda Smith, Lucas Bronicki, Olga JarinovaA cohort of 1,242 individuals tested in a clinical diagnostic laboratory was used to test whether the “Filtering Allele Frequencies” (FAFs)-based framework, recently recommended for MHY7-associated cardiomyopathy, is extendable to 45 cardiomyopathy genes. Statistical a...
Source: The Journal of Molecular Diagnostics - April 25, 2019 Category: Pathology Source Type: research

Multiplex Solid-Phase Melt Curve Analysis for the Point-of-Care Detection of HIV-1 Drug Resistance
Publication date: Available online 23 April 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Dana S. Clutter, Gelareh Mazarei, Ruma Sinha, Justen Manasa, Janin Nouhin, Ellen LaPrade, Sara Bolouki, Philip L. Tzou, Jessica Hannita-Hui, Malaya K. Sahoo, Peter Kuimelis, Robert G. Kuimelis, Benjamin A. Pinsky, Gary K. Schoolnik, Arjang Hassibi, Robert W. ShaferA point-of-care HIV-1 genotypic resistance assay that could be performed during a clinic visit would enable care providers to make informed treatment decisions for patients starting therapy or experiencing virological failure on therapy. The main challenge for s...
Source: The Journal of Molecular Diagnostics - April 24, 2019 Category: Pathology Source Type: research

Clinical validation of a cell-free DNA gene panel
We describe herein the development and clinical validation of a 28 gene cell-free DNA panel that targets the most common genetic alterations in solid tumors. Bioinformatic and variant filtering solutions were developed to improve test sensitivity and specificity. The panel and these tools were used to analyze commercially available controls, allowing establishment of a limit of detection allele frequency cutoff of 0.25%, with 100% (95% CI: 81.5% to 100%) specificity and 89.8% (95% CI: 81.0% to 94.9%) sensitivity. In addition, we analyzed a total of 163 blood samples from patients with metastatic cancer (N=123) and demonstr...
Source: The Journal of Molecular Diagnostics - April 24, 2019 Category: Pathology Source Type: research

An effective strategy to eliminate inherent cross-contamination in mtDNA next-generation sequencing of multiple samples
In this study, a novel sequencing strategy based on a unique double-barcode design was established. The results showed that when single barcode-based analysis strategy was used, cross-contamination level of 20 DNA samples ranged from 0.27% to 11.90% on Hiseq 2500 and from 0.93% to 17.70% on Hiseq X ten, whereas double barcode–based strategy could effectively eliminate cross-contamination. Moreover, the data indicated that cross-contamination was mainly derived from capture process and significantly affected by different NGS platforms. In addition, contamination level was negatively related to sequencing depth. Moreov...
Source: The Journal of Molecular Diagnostics - April 24, 2019 Category: Pathology Source Type: research

A reference system for BRCA mutation detection based on next-generation sequencing in the Chinese population
This study was performed to establish a reference system for performance evaluation of BRCA genetic testing and variant interpretation, which includes interpretation rules, reference materials (RMs), and a reference database (RD). BRCA1/2 mutations identified in cell lines and clinical cases were selected to establish RMs. All mutations were detected by NGS and validated by Sanger sequencing. Variant call format files and standard variant data sets were collected and annotated to build the RD. Participant laboratories were invited to validate this reference system. Interpretation rules for BRCA variants in the Chinese popu...
Source: The Journal of Molecular Diagnostics - April 24, 2019 Category: Pathology Source Type: research

Editorial Board
Publication date: May 2019Source: The Journal of Molecular Diagnostics, Volume 21, Issue 3Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - April 24, 2019 Category: Pathology Source Type: research

Table of Contents
Publication date: May 2019Source: The Journal of Molecular Diagnostics, Volume 21, Issue 3Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - April 24, 2019 Category: Pathology Source Type: research

Personalized Chimerism Test that Uses Selection of Short Tandem Repeat or Quantitative PCR Depending on Patient's Chimerism Status
Publication date: May 2019Source: The Journal of Molecular Diagnostics, Volume 21, Issue 3Author(s): Jennifer Tyler, Lorie Kumer, Carolyn Fisher, Heather Casey, Hiroko ShikeChimerism testing is used to monitor engraftment and risk of relapse after allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Although short tandem repeat (STR) method is widely used among clinical laboratories, quantitative PCR (qPCR) provides better sensitivity (0.1%) than STR (1% to 5%) but is less accurate than STR for patients in mixed chimerism. qPCR chimerism allows evaluation of residual recipient cells as a surroga...
Source: The Journal of Molecular Diagnostics - April 24, 2019 Category: Pathology Source Type: research

Tumor Heterogeneity Index to detect HER2 amplification by next-generation sequencing: A direct comparison study with immunohistochemistry
Publication date: Available online 22 April 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Sangjoon Choi, Jinah Chu, Binnari Kim, Sang Yun Ha, Seung Tae Kim, Jeeyun Lee, Won Ki Kang, Heewon Han, Insuk Sohn, Kyoung-Mee KimIntratumoral heterogeneity of HER2 is common in gastric cancer (GC). However, a direct comparison between the results of HER2 immunohistochemistry (IHC) and next-generation sequencing (NGS)-based cancer panel tests has not been explored in GC. We aimed to determine optimal thresholds of HER2 overexpression to be detected by NGS with the data of 168 metastatic GC cases with known expression leve...
Source: The Journal of Molecular Diagnostics - April 23, 2019 Category: Pathology Source Type: research

Analytical validation of a highly sensitive, multiplexed chronic myeloid leukemia monitoring system targeting BCR-ABL1 RNA
This study describes the analytical performance of the QuantideX qPCR BCR-ABL IS Kit, the first Federal Drug Administration–cleared assay designed to monitor BCR-ABL1 fusion transcripts isolated from peripheral blood specimens from patients with chronic myeloid leukemia. This multiplex RT-qPCR assay amplifies both e13a2 and e14a2 major BCR-ABL1 transcripts and the reference target ABL1. The test results are provided in international scale (IS) values by incorporating armored RNA-based calibrators that have defined IS values tied directly to the WHO BCR-ABL1 Primary Reference Materials, without the necessity of determ...
Source: The Journal of Molecular Diagnostics - April 23, 2019 Category: Pathology Source Type: research

Leveraging Human Microbiome Features to Diagnose and Stratify Children with Irritable Bowel Syndrome
Publication date: Available online 17 April 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Emily B. Hollister, Numan Oezguen, Bruno P. Chumpitazi, Ruth Ann Luna, Erica M. Weidler, Michelle Rubio-Gonzales, Mahmoud Dahdouli, Julia L. Cope, Toni-Ann Mistretta, Sabeen Raza, Ginger A. Metcalf, Donna M. Muzny, Richard A. Gibbs, Joseph F. Petrosino, Margaret Heitkemper, Tor C. Savidge, Robert J. Shulman, James VersalovicAccurate diagnosis and stratification of children with irritable bowel syndrome (IBS) remain challenging. Given the central role of recurrent abdominal pain in IBS, we evaluated the relationships of pe...
Source: The Journal of Molecular Diagnostics - April 18, 2019 Category: Pathology Source Type: research

Practical Bioinformatic DNA-Sequencing Pipeline for Detecting Oncogene Amplification and EGFRvIII Mutational Status in Clinical Glioblastoma Samples
Publication date: Available online 15 April 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Michael L. Miller, Jessica Tome-Garcia, Aneta Waluszko, Tatyana Sidorenko, Chitra Kumar, Fei Ye, Nadejda M. TsankovaGlioblastoma is a malignant brain tumor with dismal prognosis. Oncogenic mutations in glioblastoma frequently affect receptor tyrosine kinase pathway components that are challenging to quantify because of heterogeneous expression. EGFRvIII, a common oncogenic receptor tyrosine kinase mutant protein in glioblastoma, potentiates tumor malignancy and is an emerging tumor-specific immunotarget, underlining the n...
Source: The Journal of Molecular Diagnostics - April 16, 2019 Category: Pathology Source Type: research

Highly Multiplexed Fluorescence in Situ Hybridization for in Situ Genomics
Publication date: Available online 9 March 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Maristela L. Onozato, Clarence Yapp, Douglas Richardson, Tilak Sundaresan, Varun Chahal, Jesse Lee, James P. Sullivan, Marisa W. Madden, Hyo S. Shim, Mathew Liebers, Quan Ho, Shyamala Maheswaran, Daniel A. Haber, Zongli Zheng, Brian Clancy, Hunter L. Elliott, Jochen K. Lennerz, A. John IafrateThe quantification of changes in gene copy number is critical to our understanding of tumor biology and for the clinical management of cancer patients. DNA fluorescence in situ hybridization is the gold standard method to detect copy ...
Source: The Journal of Molecular Diagnostics - March 23, 2019 Category: Pathology Source Type: research

VarGrouper: A Bioinformatic Tool for Local Haplotyping of Deletion–Insertion Variants from Next-Generation Sequencing Data after Variant Calling
Publication date: Available online 20 February 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Ryan J. Schmidt, Allison Macleay, Long Phi LeAccurate genetic variant representation through nomenclature and annotation is essential for understanding functional consequence and properly noting the presence of variants across time, assays, and laboratories. Current variant calling algorithms detect single deletion–insertion variants as multiple indel and/or substitution variants from next-generation sequencing data. Consequently, these variants are separately annotated in bioinformatics pipelines, leading to ina...
Source: The Journal of Molecular Diagnostics - March 13, 2019 Category: Pathology Source Type: research

Panel-Based Nuclear and Mitochondrial Next-Generation Sequencing Outcomes of an Ethnically Diverse Pediatric Patient Cohort with Mitochondrial Disease
This study contributes to the lacking knowledge on MD aetiology in an understudied, ethnically diverse population, highlights inconsistencies in genotype-phenotype correlations, and proposes future directions of diagnostic approaches in such patient populations. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - March 13, 2019 Category: Pathology Source Type: research

A new fast phasing method based on haplotype subtraction
Publication date: Available online 11 March 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Evelina Mocci, Marija Debeljak, Alison P. Klein, James R. EshlemanAbstractWe developed a novel phasing approach, based solely on molecules and genotype frequency, and that does not rely on inference of new alleles. We initiated the project because of errors that were detected in the phased 1000 genomes data. The algorithm first combined identical genotypes into clusters and ranked them by descending frequency. Using alleles defined in homozygotes, it combined them to produce expected genotypes that were dismissed, and sub...
Source: The Journal of Molecular Diagnostics - March 13, 2019 Category: Pathology Source Type: research

Validated Reference Panel from renewable source of genomic DNA available for standardization of blood group genotyping
Publication date: Available online 12 March 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Evgeniya Volkova, Emilia Sippert, Meihong Liu, Teresita Mercado, Gregory A. Denomme, Orieji Illoh, Zhugong Liu, Maria Rios, Collaborative Study GroupAbstractExtended blood group genotyping is an invaluable tool used for prevention of alloimmunization. Genotyping is particularly suitable when antigens are weak, specific antisera are unavailable, or accurate phenotyping is problematic due to a disease state or recent transfusions. Additionally, genotyping facilitates establishment of mass-scale patient-matched donor databas...
Source: The Journal of Molecular Diagnostics - March 13, 2019 Category: Pathology Source Type: research

Highly Multiplexed FISH for in Situ Genomics
Publication date: Available online 9 March 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Maristela L. Onozato, Clarence Yapp, Douglas Richardson, Tilak Sundaresan, Varun Chahal, Jesse Lee, James P. Sullivan, Marisa W. Madden, Hyo Sup Shim, Mathew Liebers, Quan Ho, Shyamala Maheswaran, Daniel A. Haber, Zongli Zheng, Brian Clancy, Hunter L. Elliott, Jochen K. Lennerz, A. John IafrateThe quantification of changes in gene copy number is critical to our understanding of tumor biology and for the clinical management of cancer patients. DNA fluorescence in situ hybridization is the gold standard method to detect copy...
Source: The Journal of Molecular Diagnostics - March 11, 2019 Category: Pathology Source Type: research

Genomic Analysis of Circulating Tumor DNA Using a Melanoma-Specific UltraSEEK Oncogene Panel
Publication date: Available online 5 February 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Elin S. Gray, Tom Witkowski, Michelle Pereira, Leslie Calapre, Karl Herron, Darryl Irwin, Brett Chapman, Muhammad A. Khattak, Jeanette Raleigh, Athena Hatzimihalis, Jonathan Cebon, Shahneen Sandhu, Grant A. McArthur, Michael Millward, Melanie Ziman, Alexander Dobrovic, Stephen Q. WongThe analysis of circulating tumor DNA provides a minimally invasive molecular interrogation that has the potential to guide treatment selection and disease monitoring. Here, the authors evaluated a custom UltraSEEK melanoma panel for the Ma...
Source: The Journal of Molecular Diagnostics - March 9, 2019 Category: Pathology Source Type: research

Designing and Implementing NGS Tests for Inherited Disorders: A Practical Framework with Step-by-Step Guidance for Clinical Laboratories
Publication date: Available online 31 December 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Avni Santani, Birgitte B. Simen, Marian Briggs, Matthew Lebo, Jason D. Merker, Marina Nikiforova, Patricia Vasalos, Karl Voelkerding, John Pfeifer, Birgit FunkeComprehensive next-generation sequencing (NGS) tests are increasingly used as first-line tests in the evaluation of patients with suspected heritable disease. Despite major technical simplifications, these assays still pose significant challenges for molecular testing laboratories. Existing professional guidelines and recommendations provide a framework for labo...
Source: The Journal of Molecular Diagnostics - March 4, 2019 Category: Pathology Source Type: research

Correction
Publication date: March 2019Source: The Journal of Molecular Diagnostics, Volume 21, Issue 2Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - February 28, 2019 Category: Pathology Source Type: research

Editorial Board
Publication date: March 2019Source: The Journal of Molecular Diagnostics, Volume 21, Issue 2Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - February 28, 2019 Category: Pathology Source Type: research

Table of Contents
Publication date: March 2019Source: The Journal of Molecular Diagnostics, Volume 21, Issue 2Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - February 28, 2019 Category: Pathology Source Type: research

Targeted RNA Sequencing in Non–Small Cell Lung Cancer
Publication date: March 2019Source: The Journal of Molecular Diagnostics, Volume 21, Issue 2Author(s): Lauren L. Ritterhouse (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - February 28, 2019 Category: Pathology Source Type: research

Establishment of Immunoglobulin Heavy (IGH) Chain Clonality Testing by Next-Generation Sequencing for Routine Characterization of B-Cell and Plasma Cell Neoplasms
Publication date: March 2019Source: The Journal of Molecular Diagnostics, Volume 21, Issue 2Author(s): Maria E. Arcila, Wayne Yu, Mustafa Syed, Hannah Kim, Lidia Maciag, JinJuan Yao, Caleb Ho, Kseniya Petrova, Christine Moung, Paulo Salazar, Ivelise Rijo, Tessara Baldi, Ahmet Zehir, Ola Landgren, Jae Park, Mikhail Roshal, Ahmet Dogan, Khedoudja NafaImmunoglobulin heavy chain (IGH) clonality testing by next-generation sequencing (NGS) offers unique advantages over current low-throughput methods in the assessment of B-cell lineage neoplasms. Clinical use remains limited because assays are not standardized and validation/impl...
Source: The Journal of Molecular Diagnostics - February 28, 2019 Category: Pathology Source Type: research

Reviewer Acknowledgment
Publication date: March 2019Source: The Journal of Molecular Diagnostics, Volume 21, Issue 2Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - February 28, 2019 Category: Pathology Source Type: research

Personalized chimerism test: selection of short tandem repeat or quantitative PCR depending on patient’s chimerism status
Publication date: Available online 20 February 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Jennifer Tyler, Lorie Kumer, Carolyn Fisher, Heather Casey, Hiroko ShikeAbstractChimerism testing is used to monitor engraftment and risk of relapse after allogeneic hematopoietic stem cell transplant for hematological malignancy. Although short tandem repeat (STR) method is widely used among clinical laboratories, quantitative PCR (qPCR) provides better sensitivity (0.1%) than STR (1% to 5%), but is less accurate than STR for patients in mixed chimerism. qPCR chimerism test allows evaluation of residual recipient cell...
Source: The Journal of Molecular Diagnostics - February 21, 2019 Category: Pathology Source Type: research

A Model Information Management Plan for Molecular Pathology Sequence Data Using Standards: From Sequencer to Electronic Health Record
Publication date: Available online 20 February 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Walter S. Campbell, Alexis B. Carter, Allison M. Cushman-Vokoun, Timothy C. Greiner, Rajesh C. Dash, Mark Routbort, Monica E. de Baca, James R. CampbellIncorporating genetic variant data into the electronic health record (EHR) in discrete computable fashion has vexed the informatics community for years. Genetic sequence test results are typically communicated by the molecular laboratory and stored in the EHR as textual documents. Although text documents are useful for human readability and initial use, they are not con...
Source: The Journal of Molecular Diagnostics - February 20, 2019 Category: Pathology Source Type: research

VarGrouper – a Bioinformatic Tool for Local Haplotyping of Deletion-Insertion Variants from Next-generation Sequencing Data Post Variant Calling
Publication date: Available online 20 February 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Ryan J. Schmidt, Allison Macleay, Long Phi LeAbstractAccurate genetic variant representation through nomenclature and annotation is essential for understanding functional consequence and properly noting the presence of variants across time, assays, and laboratories. Current variant calling algorithms detect single deletion-insertion variants as multiple indel and/or substitution variants from next-generation sequencing data. Consequently, these variants are separately annotated in bioinformatics pipelines, leading to i...
Source: The Journal of Molecular Diagnostics - February 20, 2019 Category: Pathology Source Type: research

Analytical Validation of Variants to Aid in Genotype-Guided Therapy for Oncology
Publication date: Available online 20 February 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Marelize Swart, Wesley M. Stansberry, Victoria M. Pratt, Elizabeth B. Medeiros, Patrick J. Kiel, Fei Shen, Bryan P. Schneider, Todd C. SkaarThe Clinical Laboratory Improvement Amendments (CLIA) of 1988 requires that pharmacogenetic genotyping methods need to be established according to technical standards and laboratory practice guidelines before testing can be offered to patients. Testing methods for variants in ABCB1, CBR3, COMT, CYP3A7, C8ORF34, FCGR2A, FCGR3A, HAS3, NT5C2, NUDT15, SBF2, SEMA3C, SLC16A5, SLC28A3, SO...
Source: The Journal of Molecular Diagnostics - February 20, 2019 Category: Pathology Source Type: research

Rational “Error Elimination” Approach to Evaluating Molecular Barcoded Next-Generation Sequencing Data Identifies Low-Frequency Mutations in Hematologic Malignancies
In this study, we evaluated the parameters that are critical to the use of molecular barcodes in next-generation sequencing for genotyping clinical specimens from patients with hematologic malignancies. The uniform incorporation of molecular barcodes into DNA templates through PCR was found to be critical and the extent of uniformity was governed by multiple interdependent variables. An error elimination strategy was developed for removing sequencing background errors by using molecular barcode sequence information as an alternative to the traditional error correction approach. This approach was successfully used to identi...
Source: The Journal of Molecular Diagnostics - February 20, 2019 Category: Pathology Source Type: research

A Novel Approach to Detect Programed Death Ligand 1 (PD-L1) Status and Multiple Tumor Mutations Using a Single Non–Small-Cell Lung Cancer (NSCLC) Bronchoscopy Specimen
Publication date: Available online 13 February 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Amanda Vannitamby, Shona Hendry, Tanvi Makadia, Janine Danks, John Slavin, Louis Irving, Daniel Steinfort, Steven BozinovskiMultiple biomarkers are under evaluation to guide the use of immune checkpoint inhibitors in non–small-cell lung cancer (NSCLC), including programed death ligand 1 (PD-L1) tumor cell staining. We have developed a new approach that accurately quantifies PD-L1 status and identifies multiple mutations by using a single bronchoscopy specimen. A novel molecular marker was identified to detect the...
Source: The Journal of Molecular Diagnostics - February 13, 2019 Category: Pathology Source Type: research

Genetic Diagnostic Testing for Inherited Cardiomyopathies: Considerations for Offering Multi-Gene Tests in a Health Care Setting
Publication date: Available online 4 February 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Hussein Daoud, Mahdi Ghani, Landry Nfonsam, Ryan Potter, Shelley Ordorica, Virginia Haslett, Nathaniel Santos, Heather Derksen, Donelda Lahey, Martha McGill, Vanessa Trudel, Brittany Antoniuk, Nasim Vasli, Caitlin Chisholm, Gabrielle Mettler, Elizabeth Sinclair-Bourque, Jean McGowan-Jordan, Amanda Smith, Robert Roberts, Olga JarinovaAbstractInherited cardiomyopathies (ICs) are a major cause of heart disease. Given their marked clinical and genetic heterogeneity, the content and clinical utility of IC multi-gene panels h...
Source: The Journal of Molecular Diagnostics - February 6, 2019 Category: Pathology Source Type: research

Genomic Analysis of Circulating Tumor DNA Using a Melanoma-Specific UltraSEEK Oncogene Panel
Publication date: Available online 5 February 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Elin S. Gray, Tom Witkowski, Michelle Pereira, Leslie Calapre, Karl Herron, Darryl Irwin, Brett Chapman, Muhammad A. Khattak, Jeanette Raleigh, Athena Hatzimihalis, Jonathan Cebon, Shahneen Sandhu, Grant A. McArthur, Michael Millward, Melanie Ziman, Alexander Dobrovic, Stephen Q. WongThe analysis of circulating tumor DNA (ctDNA) provides a minimally-invasive molecular interrogation that has the potential to guide treatment selection and disease monitoring. Here, we evaluated a custom UltraSEEK melanoma panel for the Mas...
Source: The Journal of Molecular Diagnostics - February 6, 2019 Category: Pathology Source Type: research

Optimization of next-generation sequencing technologies for von Hippel Lindau (VHL) mosaic mutation detection and development of confirmation methods
In conclusion, NGS technologies combined with SNaPshot or droplet digital PCR allow the detection and confirmation of mosaic mutations in a clinical laboratory setting. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - February 6, 2019 Category: Pathology Source Type: research

Combined Targeted Resequencing of Cytosine DNA Methylation and Mutations of DNA Repair Genes with Potential Use for Poly(ADP-Ribose) Polymerase 1 Inhibitor Sensitivity Testing
Publication date: Available online 19 December 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Christina Grimm, Axel Fischer, Angela M. Farrelly, Roshni Kalachand, Roberta Castiglione, Elena Wasserburger, Michelle Hussong, Anne M. Schultheis, Janine Altmüller, Holger Thiele, Hans C. Reinhardt, Kai Hauschulz, Bryan T. Hennessy, Ralf Herwig, Matthias Lienhard, Reinhard Buettner, Michal R. SchweigerCurrent molecular tumor diagnostics encompass panel sequencing to detect mutations, copy number alterations, and rearrangements. However, tumor suppressor genes can also be inactivated by methylation within their pr...
Source: The Journal of Molecular Diagnostics - January 29, 2019 Category: Pathology Source Type: research

Considerations for Genomic Data Privacy and Security When Working in the Cloud
Publication date: Available online 28 January 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Alexis B. CarterAbstractNext-generation sequencing produces large amounts of data. The complexity and data management issues associated with next-generation sequencing have led many laboratories to turn to cloud services, especially when internal information technology infrastructure is inadequate to support data requirements. In addition, public cloud repositories of variants are being increasingly utilized, and their data sets are being populated through crowdsourcing submissions of human genetic variation identified ...
Source: The Journal of Molecular Diagnostics - January 29, 2019 Category: Pathology Source Type: research