Bench to Bedside
In this issue of The Journal of Molecular Diagnostics, Wan et al describe an alternative method in the diagnosis of Leber hereditary optic neuropathy (LHON) variants using a rapid and convenient system with a low limit of detection that can be readily integrated into clinical practice.1 This method utilizes clustered regularly interspaced short palindromic repeats (CRISPR)/Cas –based nucleic acid detection technology combined with enzymatic recombinase amplification to provide a visual detection system for the three LHON primary variants. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 29, 2023 Category: Pathology Authors: Benjamin Hilton Tags: Commentary Source Type: research
Editorial Board
The Journal of Molecular Diagnostics, the official publication of the Association for Molecular Pathology, co-owned by the American Society for Investigative Pathology and published by Elsevier, Inc., seeks to publish highquality original papers on scientific advances in the translation and validation of molecular discoveries in medicine into the clinical diagnostic setting, and the description and application of technological advances in the field of molecular diagnostic medicine. The editors welcome for review articles that contain: novel discoveries or clinicopathologic correlations including studies in oncology, infect...
Source: Journal of Molecular Diagnostics - July 29, 2023 Category: Pathology Source Type: research
Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 29, 2023 Category: Pathology Source Type: research
Implementation of DNA Methylation Array Profiling in Pediatric Central Nervous System Tumors
DNA methylation array profiling for classifying pediatric central nervous system (CNS) tumors is a valuable adjunct to histopathology. However, unbiased prospective and interlaboratory validation studies have been lacking. The AIM BRAIN diagnostic trial involving 11 pediatric cancer centers in Australia and New Zealand was designed to test the feasibility of routine clinical testing and ran in parallel with the Molecular Neuropathology 2.0 (MNP2.0) study at Deutsches Krebsforschungszentrum (German Cancer Research Center). (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 28, 2023 Category: Pathology Authors: Christine L. White, Kathryn M. Kinross, Molly K. Buntine, Elnaz Rasouli, Robyn Strong, Janelle M. Jones, Jason E. Cain, Dominik Sturm, Felix Sahm, David T.W. Jones, Stefan M. Pfister, Thomas Robertson, Colleen D'Arcy, Michael L. Rodriguez, Jason M. Dyke, Tags: Regular article Source Type: research
Formalin-Fixed, Paraffin-Embedded –Targeted Locus Capture
Chromosomal rearrangements are important drivers in cancer, and their robust detection is essential for diagnosis, prognosis, and treatment selection, particularly for bone and soft tissue tumors. Current diagnostic methods are hindered by limitations, including difficulties with multiplexing targets and poor quality of RNA. A novel targeted DNA-based next-generation sequencing method, formalin-fixed, paraffin-embedded –targeted locus capture (FFPE-TLC), has shown advantages over current diagnostic methods when applied on FFPE lymphomas, including the ability to detect novel rearrangements. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 28, 2023 Category: Pathology Authors: Ellen Stelloo, Ruud W.J. Meijers, Joost F. Swennenhuis, Amin Allahyar, Karima Hajo, Mario Cangiano, Wendy W.J. de Leng, Sjoerd van Helvert, Joni Van der Meulen, David Creytens, L éon C. van Kempen, Anne-Marie Cleton-Jansen, Judith V.M.G. Bovee, Wouter de Tags: Regular article Source Type: research
FFPE-TLC: an NGS technology for accurate DNA-based gene fusion detection in bone and soft tissue tumors
Chromosomal rearrangements are important drivers in cancer and their robust detection is essential for diagnosis, prognosis and treatment selection, particularly for bone and soft tissue tumors. Current diagnostic methods are hindered by limitations including difficulties with multiplexing targets and poor quality of RNA. A novel targeted DNA-based NGS method ‘FFPE-TLC’ has shown advantages over current diagnostic methods when applied on FFPE lymphomas, including the ability to detect novel rearrangements. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 28, 2023 Category: Pathology Authors: Ellen Stelloo, Ruud W.J. Meijers, Joost F. Swennenhuis, Amin Allahyar, Karima Hajo, Mario Cangiano, Wendy W.J. de Leng, Sjoerd van Helvert, Joni Van der Meulen, David Creytens, L éon C. van Kempen, Anne-Marie Cleton-Jansen, Judith V.M.G. Bovee, Wouter de Tags: Regular Article Source Type: research
Implementation of DNA methylation array profiling in pediatric central nervous system tumors - the AIM BRAIN Project: an Australian and New Zealand Children ’s Haematology and Oncology (ANZCHOG) Group study.
DNA methylation array profiling for classifying pediatric central nervous system (CNS) tumors is a valuable adjunct to histopathology. However, unbiased prospective and inter-laboratory validation studies have been lacking. The AIM BRAIN (AB) diagnostic trial involving 11 pediatric cancer centers in Australia and New Zealand was designed to test the feasibility of routine clinical testing and ran in parallel with the Molecular Neuropathology 2.0 (MNP2.0) study at Deutsches Krebsforschungszentrum (DKFZ) (German Cancer Centre Heidelberg, Germany). (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 28, 2023 Category: Pathology Authors: Christine L. White, Kathryn M. Kinross, Molly K. Buntine, Elnaz Rasouli, Robyn Strong, Janelle M. Jones, Jason E. Cain, Dominik Sturm, Felix Sahm, David T.W. Jones, Stefan M. Pfister, Thomas Robertson, Colleen D ’Arcy, Michael L. Rodriguez, Jason M. Dyk Tags: Regular Article Source Type: research
The Genetic Testing Reference Materials Coordination Program
The Genetic Testing Reference Materials (GeT-RM) Coordination Program was established in 2004 at the CDC, which has consistently operated collaboratively with the genetic testing community to characterize publicly available genomic DNA reference materials.1 The Program was initially centered on characterizing reference materials for mendelian genetic disorders commonly tested by clinical laboratories; however, in 2010, the GeT-RM Program reported the first collaborative effort to characterize five clinically actionable genes implicated in interindividual drug response variability: CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A...
Source: Journal of Molecular Diagnostics - July 20, 2023 Category: Pathology Authors: Stuart A. Scott Tags: Commentary Source Type: research
The Genetic Testing Reference Materials (GeT-RM) Coordination Program: Over 10 years of support for pharmacogenomic testing
The Genetic Testing Reference Materials (GeT-RM) Coordination Program was established in 2004 at the Centers for Disease Control and Prevention (CDC), which has consistently operated collaboratively with the genetic testing community to characterize publicly available genomic DNA reference materials.1 The Program was initially centered on characterizing reference materials for Mendelian genetic disorders commonly tested by clinical laboratories; however, in 2010 the GeT-RM reported the first collaborative effort to characterize five clinically actionable genes implicated in interindividual drug response variability: CYP2D6...
Source: Journal of Molecular Diagnostics - July 20, 2023 Category: Pathology Authors: Stuart A. Scott Tags: Commentary Source Type: research
Evaluation of a Zoonotic Orthopoxvirus PCR Assay for the Detection of Monkeypox Virus Infection
An epidemic caused by an outbreak of monkeypox (mpox) in May 2022 rapidly spread internationally, requiring an urgent response from the clinical diagnostics community. A detailed description of the clinical validation and implementation of a laboratory-developed real-time PCR test for detecting nonvariola Orthopoxvirus-specific DNA based on the newly designed RealStar Zoonotic Orthopoxvirus assay is presented. The validation was performed using an accuracy panel (n = 97) comprising skin lesion swabs in universal transport media and from mpox virus genomic DNA spiked into pooled mpox virus–negative remnant universal tr...
Source: Journal of Molecular Diagnostics - July 18, 2023 Category: Pathology Authors: Priya Velu, John Sipley, Jamie Marino, Sanjiv Ghanshani, Georgi Lukose, Lin Cong, Liliana Serrano, Thanh Ly, Raymond K. Yeh, Fan Wu, Mahesh Mansukhani, Greg Berry, Hanna Rennert Tags: Regular article Source Type: research
Evaluation of a Zoonotic Orthopoxvirus PCR Assay for the Detection of Mpox Virus Infection
An epidemic caused by an outbreak of mpox in May 2022 rapidly spread internationally, requiring an urgent response from the clinical diagnostics community. A detailed description of the clinical validation and implementation of a laboratory-developed real-time PCR (rt-PCR) test for detecting non-variola Orthopoxvirus (OPXV) specific DNA based on the newly designed RealStar Zoonotic Orthopoxvirus (altona Diagnostics, Hamburg, Germany) assay is presented. The validation was performed using an accuracy panel (n=97) comprising skin lesion swabs in universal transport media (UTM) and from Mpox virus (MPXV) genomic DNA spiked in...
Source: Journal of Molecular Diagnostics - July 18, 2023 Category: Pathology Authors: Priya Velu, John Sipley, Jamie Marino, Sanjiv Ghanshani, Georgi Lukose, Lin Cong, Liliana Serrano, Thanh Ly, Raymond K. Yeh, Fan Wu, Mahesh Mansukhani, Greg Berry, Hanna Rennert Tags: Regular Article Source Type: research
EuroClonality-NGS Recommendations for Evaluation of B-Cell Clonality Analysis by Next-Generation Sequencing
Next-generation sequencing (NGS)-based clonality analysis allows in-depth assessment of the clonal composition of a sample with high sensitivity for detecting small clones. Within the EuroClonality –NGS working group, a protocol for NGS Ig clonality analysis was developed and validated previously. This NGS-based approach was designed to generate small amplicons, making it suitable for samples with suboptimal DNA quality, especially material derived from formalin-fixed, paraffin-embedded tiss ue. Using expert assessment of NGS Ig clonality results as a reference, a structured algorithmic approach to the assessment of NGS-...
Source: Journal of Molecular Diagnostics - July 17, 2023 Category: Pathology Authors: Michiel van den Brand, Markus M öbs, Franziska Otto, Leonie I. Kroeze, David Gonzalez-de Castro, Kostas Stamatopoulos, Frederic Davi, Clotilde Bravetti, P. Martijn Kolijn, Elisavet Vlachonikola, J. Peter Stewart, Christiane Pott, Michael Hummel, Nikos Da Tags: Regular article Source Type: research
A Well-Curated Cost-Effective Next-Generation Sequencing Panel Identifies a Diverse Landscape of Pathogenic and Novel Germline Variants in a Bone Marrow Failure Cohort in a Resource-Constraint Setting
The current study is a 4-year experience in diagnosis and screening of inherited and immune bone marrow failure cases using a targeted sequencing panel. A total of 171 cases underwent targeted next-generation sequencing and were categorized as suspected inherited bone marrow failure syndrome (IBMFS) group (106; 62%) and immune/idiopathic aplastic anemia (IAA) group (65; 38%) based on clinical and laboratory criteria. A total of 110 (64%) were pediatric (aged 0 to 12 years) patients and 61 (36%) were adolescent and adult (aged 13 to 47 years) patients. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 17, 2023 Category: Pathology Authors: Swetha Pallavelangini, Gnanamani Senguttuvan, Prateek Bhatia, Prashant Chhabra, Minu Singh, Alka Khadwal, Arihant Jain, Pankaj Sharma, Rozy Thakur, Sreejesh Sreedharanunni, Deepak Bansal, Richa Jain, Srinivasan Peyam, Sonali Mohapatra, Ankur Jindal, Deept Tags: Regular article Source Type: research
A well curated cost-effective next generation sequencing panel identifies a diverse landscape of pathogenic and novel germline variants in bone marrow failure cohort in a resource constraint setting
Current study is a 4 year experience in diagnosis and screening of inherited and immune bone marrow failure cases using a targeted sequencing panel. A total of 171 cases underwent targeted NGS and were categorized as suspected inherited bone marrow failure syndrome (IBMFS) group (106; 62%) and immune/idiopathic aplastic anemia (IAA) group (65; 38%) based on clinical and laboratory criteria. 110 (64%) were pediatric (0-12 years) and 61 (36%) adolescent and adults (13-47 years). In suspected IBMFS group, 47 (44%) and in IAA group, 8 (12%) revealed a likely germline pathogenic variation. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 17, 2023 Category: Pathology Authors: Swetha Pallavelangini, Gnanamani Senguttuvan, Prateek Bhatia, Prashant Chhabra, Minu Singh, Alka Khadwal, Arihant Jain, Pankaj Sharma, Rozy Thakur, Sreejesh Sreedharanunni, Deepak Bansal, Richa Jain, Srinivasan Peyam, Sonali Mohapatra, Ankur Jindal, Deept Tags: Regular Article Source Type: research
EuroClonality-NGS recommendations for evaluation of B cell clonality analysis by next-generation sequencing – a structured approach with the DEPART algorithm
Next generation sequencing (NGS)-based clonality analysis allows in-depth assessment of the clonal composition of a sample with a high sensitivity for detecting small clones. Within the EuroClonality-NGS working group, a protocol for NGS IG clonality analysis has been previously developed and validated. This NGS-based approach was designed to generate small amplicons, making it suitable for samples with suboptimal DNA quality, especially material derived from formalin-fixed paraffin-embedded tissue. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 17, 2023 Category: Pathology Authors: Michiel van den Brand, Markus Mobs, Franziska Otto, Leonie I. Kroeze, David Gonzalez-de Castro, Kostas Stamatopoulos, Frederic Davi, Clotilde Bravetti, P. Martijn Kolijn, Elisavet Vlachonika, J Peter Stewart, Christiane Pott, Michael Hummel, Nikos Darzent Tags: Regular Article Source Type: research
