Comparing the Diagnostic Performance of Quantitative PCR, Digital Droplet PCR, and Next-Generation Sequencing Liquid Biopsies for Human Papillomavirus –Associated Cancers
Human papillomavirus (HPV)-associated cancers, including oropharyngeal squamous cell carcinoma (HPV + OPSCC), cervical cancer, and squamous cell carcinoma of the anus (HPV + SCCA), release circulating tumor HPV DNA (ctHPVDNA) into the blood. The diagnostic performance of ctHPVDNA detection depends on the approaches used and the individual assay metrics. A comparison of these approaches has no t been systematically performed to inform expected performance, which in turn affects clinical interpretation. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 14, 2023 Category: Pathology Authors: Saskia Naegele, Daniel A. Ruiz-Torres, Yan Zhao, Deborah Goss, Daniel L. Faden Tags: Regular article Source Type: research
Quantification of Measurable Residual Disease Detection by Next-Generation Sequencing –Based Clonality Testing in B-Cell and Plasma Cell Neoplasms
Next-generation sequencing (NGS)-based measurable residual disease (MRD) monitoring in post-treatment settings can be crucial for relapse risk stratification in patients with B-cell and plasma cell neoplasms. Prior studies have focused on validation of various technical aspects of the MRD assays, but more studies are warranted to establish the performance characteristics and enable standardization and broad utilization in routine clinical practice. Here, the authors describe an NGS-based IGH MRD quantification assay, incorporating a spike-in calibrator for monitoring B-cell and plasma cell neoplasms based on their unique I...
Source: Journal of Molecular Diagnostics - December 14, 2023 Category: Pathology Authors: Ying Liu, Caleb Ho, Wayne Yu, Ying Huang, Jeffrey Miller, Qi Gao, Mustafa Syed, Yuanyuan Ma, Meiyi Wang, Lidia Maciag, Kseniya Petrova-Drus, Menglei Zhu, JinJuan Yao, Chad Vanderbilt, Benjamin Durham, Jamal Benhamida, Mark D. Ewalt, Ahmet Dogan, Mikhail R Tags: Regular article Source Type: research
Comparing the Diagnostic Performance of qPCR, ddPCR, and NGS Liquid Biopsies for HPV-Associated Cancers
HPV-associated cancers, including oropharyngeal squamous cell carcinoma(HPV+OPSCC), cervical cancer(HPV+CC), and squamous cell carcinoma of the anus(HPV+SCCA), release circulating tumor HPV DNA(ctHPVDNA) into the blood. The diagnostic performance of ctHPVDNA detection depends on the approaches utilized and the individual assay metrics. A comparison of these approaches has not been systematically performed to inform expected performance, which in turn impacts clinical interpretation. A meta-analysis was performed using Ovid MEDLINE, Embase, and Web of Science Core Collection databases to assess the diagnostic accuracy of ct...
Source: Journal of Molecular Diagnostics - December 14, 2023 Category: Pathology Authors: Saskia Naegele, Daniel A. Ruiz-Torres, Yan Zhao, Deborah Goss, Daniel L. Faden Tags: Regular Article Source Type: research
Slice Testing - Considerations from Ordering to Reporting: A Joint Report of the Association for Molecular Pathology, College of American Pathologists, and National Society of Genetic Counselors
As the number of genes associated with various germline disorders continues to grow, it is becoming more difficult for clinical laboratories to maintain separate assays for interrogating disease focused gene panels. One solution to this challenge is termed slice testing, where capture backbone is utilized to analyze data specific to a set of genes, and for this paper, we will focus on exome. A key advantage to this strategy is greater flexibility by adding genes as they become associated with disease or the ability to accommodate specific provider requests. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 14, 2023 Category: Pathology Authors: Jeffrey A. SoRelle, Birgit H. Funke, Celeste C. Eno, Jianling Ji, Avni Santani, Pinar Bayrak-Toydemir, Megan Wachsmann, Karen E. Wain, Rong Mao Tags: Special Article Source Type: research
Quantification of Measurable Residual Disease Detection by Next Generation Sequencing-based Clonality Testing in B-cell and Plasma Cell Neoplasms
Next generation sequencing (NGS)-based measurable residual disease (MRD) monitoring in post-treatment settings can be crucial for relapse risk stratification in patients with B-cell and plasma cell neoplasms. Prior studies have focused on validation of various technical aspects of the MRD assays, but more studies are warranted to establish the performance characteristics and enable standardization and broad utilization in routine clinical practice. Here, we describe our approach and clinical experience with an NGS-based IGH MRD quantification assay, incorporating a spike-in calibrator for monitoring B-cell and plasma cell ...
Source: Journal of Molecular Diagnostics - December 14, 2023 Category: Pathology Authors: Ying Liu, Caleb Ho, Wayne Yu, Ying Huang, Jeffrey Miller, Qi Gao, Mustafa Syed, Yuanyuan Ma, Meiyi Wang, Lidia Maciag, Kseniya Petrova-Drus, Menglei Zhu, JinJuan Yao, Chad Vanderbilt, Benjamin Durham, Jamal Benhamida, Mark D. Ewalt, Ahmet Dogan, Mikhail R Tags: Regular Article Source Type: research
Uncovering the Genetic Etiology of Inherited Bone Marrow Failure Syndromes Using a Custom-designed Next Generation Sequencing Panel
We report the laboratory validation and clinical utility of a large custom-designed NGS panel, CHOP IBMFS panel, for the diagnosis of IBMFS in a large cohort of pediatric patients. This panel demonstrated excellent analytic accuracy with 100% sensitivity, ≥99.99% specificity, and 100% reproducibility on validation samples. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 14, 2023 Category: Pathology Authors: Fumin Lin, Kajia Cao, Fengqi Chang, Joseph H. Oved, Minjie Luo, Zhiqian Fan, Jeffrey Schubert, Jinhua Wu, Yiming Zhong, Daniel J. Gallo, Elizabeth H. Denenberg, Jiani Chen, Elizabeth A. Fanning, Michele P. Lambert, Michele E. Paessler, Lea F. Surrey, Kris Tags: Regular Article Source Type: research
Operationalizing Quality Assurance for Clinical Illumina Somatic Next-Generation Sequencing Pipelines
Quality assurance is essential for precision oncology workflows, in particular in the clinical setting. However, due to numerous variations in laboratory and bioinformatics pipelines, quality assurance practices remain non-standardized, often ad hoc, and lacking longitudinal tracking. A selected review of existing software was performed for quality control of Illumina next-generation sequencing data, focusing specifically on generalizable tools that can be integrated into any bioinformatics workflow to easily develop a quality assurance workflow with longitudinal tracking. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 9, 2023 Category: Pathology Authors: Joshua Bridgers, Kenyon Alexander, Aly Karsan Tags: Technical Advance Source Type: research
MLH1 promotor hypermethylation in colorectal and endometrial carcinomas from patients with Lynch syndrome
Screening for Lynch syndrome (LS) in colorectal cancer (CRC) and endometrial cancer (EC) patients generally involves immunohistochemical staining of the mismatch repair (MMR) proteins. In case of MLH1 protein loss, MLH1 promotor hypermethylation (MLH1-PM) testing is performed to indirectly distinguish constitutional MLH1 variants from somatic epimutations. However, in recent years a growing number of studies have reported that MLH1-PM and pathogenic constitutional MMR variants are not mutually exclusive. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 5, 2023 Category: Pathology Authors: Noah C. Helderman, Katarina D. Andini, Monique E. van Leerdam, Liselotte P. van Hest, Dani ël R. Hoekman, Aysel Ahadova, Sanne W. Bajwa - ten Broeke, Tjalling Bosse, Elise M.J. van der Logt, Floris Imhann, Matthias Kloor, Alexandra M.J. Langers, Vincent Tags: Regular Article Source Type: research
Editorial Board
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 24, 2023 Category: Pathology Source Type: research
Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 24, 2023 Category: Pathology Source Type: research
FindDNAFusion
Detection of cancer-associated gene fusions is crucial for diagnosis, prognosis, and treatment selection. Many bioinformatics tools are available for the detection of fusion transcripts by RNA sequencing, but there are fewer well-validated software tools for DNA next-generation sequencing (NGS). A 542-gene solid tumor NGS panel was designed, with exonic probes supplemented with intronic bait probes against genes commonly involved in oncogenic fusions, with a focus on lung cancer. Three software tools for the detecting gene fusions in this DNA-NGS panel were selected and evaluated. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 24, 2023 Category: Pathology Authors: Xiaokang Pan, Huolin Tu, Nehad Mohamed, Matthew Avenarius, Sean Caruthers, Weiqiang Zhao, Dan Jones Tags: Regular article Source Type: research
Droplet Digital PCR for Fast and Accurate Characterization of NF1 Locus Deletions
Neurofibromatosis type-1 is a genetic disorder caused by loss-of-function variants in the tumor-suppressor NF1. Approximately 4% to 11% of neurofibromatosis type-1 patients have a NF1 locus complete deletion resulting from nonallelic homologous recombination between low copy repeats. Codeleted genes probably account for the more severe phenotype observed in NF1-deleted patients. This genotype –phenotype correlation highlights the need for a detailed molecular description. A droplet digital PCR (ddPCR) set along the NF1 locus was designed to delimitate the three recurrent NF1 deletion breakpoints. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 24, 2023 Category: Pathology Authors: Laurence Pacot, Manuela Ye, Juliette Nectoux, Ingrid Laurendeau, Audrey Briand-Suleau, Audrey Coustier, Th éodora Maillard, Cécile Barbance, Lucie Orhant, Nicolas Vaucouleur, Hélène Blanché, Béatrice Parfait, Pierre Wolkenstein, Michel Vidaud, EURON Tags: Regular article Source Type: research
Variant Classification Discordance
An ever-growing catalog of human variants is hosted in the ClinVar database. In this database, submissions on a variant are combined into a multisubmitter record; and in the case of discordance in variant classification between submitters, the record is labeled as conflicting. We used ClinVar data to identify characteristics that would make variants more likely to be associated with the conflict class of variants. Furthermore, we used the Extreme Gradient Boosting algorithm to train classifier models to provide prediction of classification discordance for single submission variants in ClinVar database. (Source: Journal of ...
Source: Journal of Molecular Diagnostics - November 24, 2023 Category: Pathology Authors: Hamid Ghaedi, Scott K. Davey, Harriet Feilotter Tags: Regular article Source Type: research
An Exome Capture-Based RNA-Sequencing Assay for Genome-Wide Identification and Prioritization of Clinically Important Fusions in Pediatric Tumors
We report the development of an exome capture-based RNA-sequencing assay to detect recurring and novel fusions in hematologic, solid, and central nervous system tumors. The assay uses Twist Comprehensive Exome capture with either fresh or formalin-fixed samples and a bioinformatic platform that provides fusion detection, prioritization, and downstream curation. A minimum of 50 million uniquely mapped reads, a consensus read alignment/fusion calling approach using four callers (Arriba, FusionCatcher, STAR-Fusion, and Dragen), and custom software are used to integrate, annotate, and rank the candidate fusion calls. (Source: ...
Source: Journal of Molecular Diagnostics - November 24, 2023 Category: Pathology Authors: Jonathan Buckley, Ryan Schmidt, Dejerianne Ostrow, Dennis Maglinte, Moiz Bootwalla, David Ruble, Ananthanarayanan Govindarajan, Jianling Ji, Alexandra E. Kovach, Etan Orgel, Gordana Raca, Fariba Navid, Leo Mascarenhas, Bruce Pawel, Nathan Robison, Xiaowu Tags: Regular article Source Type: research
Droplet digital PCR for fast and accurate characterization of NF1 locus deletions: confirmation of the predominant maternal origin of type-1 deletions
Neurofibromatosis type 1 (NF1) is a genetic disorder caused by loss-of-function variants in the tumor-suppressor NF1. About 4-11% of NF1 patients have a NF1 locus complete deletion resulting from non-allelic homologous recombination between low copy repeats. Co-deleted genes probably account for the more severe phenotype observed in NF1-deleted patients. This genotype-phenotype correlation highlights the need for a detailed molecular description. We designed a digital droplet PCR (ddPCR) set along the NF1 locus to delimitate the three recurrent NF1 deletion breakpoints. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 24, 2023 Category: Pathology Authors: Laurence Pacot, Manuela Ye, Juliette Nectoux, Ingrid Laurendeau, Audrey Briand-Suleau, Audrey Coustier, Th éodora Maillard, Cécile Barbance, Lucie Orhant, Nicolas Vaucouleur, Hélène Blanché, Béatrice Parfait, Pierre Wolkenstein, Michel Vidaud, EURON Tags: Regular Article Source Type: research
