Minimizing sample failure rates for challenging clinical tumor samples
Identification of somatic variants in cancer by high-throughput sequencing has become common clinical practice largely because many of these variants may be predictive biomarkers for targeted therapies. However, there can be high sample quality control (QC) failure rates for some tests preventing the return of results.SLIMamp is a patented technology that has been incorporated into commercially available cancer NGS testing kits with the claimed advantage that these kits can interrogate challenging formalin-fixed paraffin-embedded tissue (FFPET) samples with low tumor purity, poor DNA quality, and/or low input DNA, resultin...
Source: Journal of Molecular Diagnostics - February 9, 2023 Category: Pathology Authors: J. Lynn Fink, Binny Jaradi, Nathan Stone, Lisa Anderson, Paul J. Leo, Mhairi Marshall, Jonathan Ellis, Paul M. Waring, Kenneth O ’Byrne Tags: Regular Article Source Type: research
Next-CLL: a new next generation sequencing-based method for assessment of IGHV gene mutational status in chronic lymphoid leukemia
Current guidelines for patients with Chronic Lymphocytic Leukemia (CLL) recommend mutation status determination of the clonotypic IGHV gene prior to treatment initiation in order to guide the choice of the first-line therapy. Currently, commercially available next-generation sequencing (NGS) solutions have technical constraints, as they necessitate at least a 2x300 bp sequencing, which restricts their use for routine practice. The cost of the commercial kits also represents an important drawback. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 9, 2023 Category: Pathology Authors: Estelle Bourbon, Kaddour Chabane, Isabelle Mosnier, Anne Bouvard, Florian Thonier, Emmanuelle Ferrant, Anne-Sophie Michallet, St éphanie Poulain, Sandrine Hayette, Pierre Sujobert, Sarah Huet Tags: Regular Article Source Type: research
Clinical Validation and Diagnostic Utility of Optical Genome Mapping in Prenatal Diagnostic Testing
The standard-of-care (SOC) diagnostic prenatal testing includes a combination of cytogenetic methods such as karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray (CMA) using either direct or cultured amniocytes or chorionic villi sampling (CVS). However, each technology has its limitations: karyotyping has a low resolution (>5Mb), FISH is targeted, and CMA does not detect balanced structural variants (SVs). These limitations necessitate the use of multiple tests, either simultaneously or sequentially to reach a genetic diagnosis. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 7, 2023 Category: Pathology Authors: Nikhil Shri Sahajpal, Ashis K. Mondal, Timothy Fee, Benjamin Hilton, Lawrence Layman, Alex R. Hastie, Alka Chaubey, Barbara R. DuPont, Ravindra Kolhe Tags: Regular Article Source Type: research
Rapid Lineage Assignment of Severe Acute Respiratory Syndrome Coronavirus 2 Cases through Automated Library Preparation, Sequencing, and Bioinformatic Analysis
This study evaluated the turnaround time, accuracy, and other quality-related parameters obtained from commercially available automated sequencing instrumentation, from analysis of continuous clinical samples obtained from January 1, 2021, to October 6, 2021. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 6, 2023 Category: Pathology Authors: Andrew J. Gorzalski, Heather Kerwin, Subhash Verma, David C. Hess, Joel Sevinsky, Kevin Libuit, Irina Vlasova-St. Louis, Danielle Siao, Lauren Siao, Diego Bunuel, Stephanie Van Hooser, Mark W. Pandori Tags: Technical advance Source Type: research
Rapid Lineage Assignment of SARS-CoV-2 Cases Through Automated Library Preparation, Sequencing and Bioinformatic Analysis
The COVID-19 pandemic has provided a stage to illustrate that there is considerable value in obtaining rapid, whole genomic information about pathogens. Herein we describe the utility of a commercially available, automated SARS-CoV-2 library preparation, genomic sequencing and a bioinformatic analysis pipeline to provide rapid, near- “real-time” SARS-CoV-2 variant description. We evaluated the turnaround time, accuracy and other quality parameters obtained from Clear Labs Dx automated sequencing instrumentation from analysis of continuous clinical samples from January 1, 2021 to October 6, 2021. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 6, 2023 Category: Pathology Authors: Andrew J. Gorzalski, Heather Kerwin, Subhash Verma, David C. Hess, Joel Sevinsky, Kevin Libuit, Irina Vlasova-St. Louis, Danielle Siao, Lauren Siao, Diego Bunuel, Stephanie Van Hooser, Mark W. Pandori Tags: Technical Advance Source Type: research
Pyrosequencing Assay for BRCA1 Methylation Analysis
Epithelial ovarian cancers (EOCs) harboring germline or somatic pathogenic variants in BRCA1 and BRCA2 genes show sensitivity to poly(ADP-ribose) polymerase inhibition. It has been suggested that BRCA1 promoter methylation is perhaps a better determinant of therapy response, because of its intrinsic dynamic feature, with respect to genomic scars or gene mutation. Conflicting evidence was reported so far, and the lack of a validated assay to measure promoter methylation was considered a main confounding factor in data interpretation. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 3, 2023 Category: Pathology Authors: Nora Sahnane, Daniela Rivera, Laura Libera, Ileana Carnevali, Barbara Banelli, Sofia Facchi, Viviana Gismondi, Michele Paudice, Gabriella Cirmena, Valerio Gaetano Vellone, Fausto Sessa, Liliana Varesco, Maria Grazia Tibiletti Tags: Regular article Source Type: research
Recurrent AKR1D1 c.580-13T > A Variant
Δ4-3-oxosteroid 5β-reductase (AKR1D1) deficiency presents with neonatal cholestasis and liver failure in early infancy and features high levels of 3-oxo-Δ4-bile acids in urine. Genetic analysis is needed for definitive diagnosis, because in the neonatal period it can be difficult to distinguish a primary from a secondary enzyme deficiency. By re-analysis of the gene-sequencing data, one AKR1D1 noncanonical splice-site variant (NM_005989.4: c.580-13T>A) with controversial pathogenicity was discovered to be enriched in eight families with clinical and biochemically confirmed AKR1D1 deficiency. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 3, 2023 Category: Pathology Authors: Jing Zhao, Yi-ling Qiu, Li Wang, Zhong-die Li, Xin-bao Xie, Yi Lu, Kenneth D.R. Setchell, Ye Cheng, Qing-he Xing, Jian-She Wang Tags: Regular article Source Type: research
Recurrent AKR1D1 c.580-13T > A variant – A cause of Δ4-3-oxosteroid-5β-reductase deficiency
Δ4-3-oxosteroid 5β-reductase (AKR1D1) deficiency presents with neonatal cholestasis and liver failure in early infancy and features high levels of 3-oxo- Δ4- bile acids in urine. Genetic analysis is needed for definitive diagnosis, because in the neonatal period it can be difficult to distinguish a primary from secondary enzyme deficiency. By re-analysis of the gene sequencing data, one AKR1D1 non-canonical splice-site variant (NM_005989.4: c.580-13T>A) with controversial pathogenicity was discovered to be enriched in 8 families with clinical and biochemically confirmed AKR1D1 deficiency. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 3, 2023 Category: Pathology Authors: Jing Zhao, Yi-ling Qiu, Li Wang, Zhong-die Li, Xin-bao Xie, Yi Lu, Kenneth DR. Setchell, Ye Cheng, Qing-he Xing, Jian-She Wang Tags: Regular Article Source Type: research
Pyrosequencing assay for BRCA1 methylation analysis: results from a cross-validation study
Epithelial Ovarian Cancers (EOCs) harboring germline or somatic pathogenic variants in BRCA1 and BRCA2 genes show sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition. It has been suggested that BRCA1 promoter methylation is perhaps a better determinant of therapy response, due to its intrinsic dynamic feature, with respect to genomic scars or gene mutation. Conflicting evidence was reported so far and the lack of a validated assay to measure promoter methylation was considered a main confounding factor in data interpretation. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 3, 2023 Category: Pathology Authors: Nora Sahnane, Daniela Rivera, Laura Libera, Ileana Carnevali, Barbara Banelli, Sofia Facchi, Viviana Gismondi, Michele Paudice, Gabriella Cirmena, Valerio Gaetano Vellone, Fausto Sessa, Liliana Varesco, Maria Grazia Tibiletti Tags: Regular Article Source Type: research
Point-of-Care Testing of Enzyme Polymorphisms for Predicting Hypnotizability and Postoperative Pain
Hypnotizability is a stable trait that moderates the benefit of hypnosis for treating pain, but limited availability of hypnotizability testing deters widespread use of hypnosis. Inexpensive genotyping of four single-nucleotide polymorphisms in the catechol-o-methyltransferase (COMT) gene was performed using giant magnetoresistive biosensors to determine if hypnotizable individuals can be identified for targeted hypnosis referrals. For individuals with the proposed optimal COMT diplotypes, 89.5% score highly on the Hypnotic Induction Profile (odds ratio, 6.12; 95% CI, 1.26–28.75), which identified 40.5% of the treatab...
Source: Journal of Molecular Diagnostics - January 23, 2023 Category: Pathology Authors: Dana L. Cortade, Jessie Markovits, David Spiegel, Shan X. Wang Tags: Regular article Source Type: research
Point of care testing of enzyme polymorphisms for predicting hypnotizability and postoperative pain
Hypnotizability is a stable trait that moderates the benefit of hypnosis for treating pain, but limited availability of hypnotizability testing deters widespread use of hypnosis. Inexpensive genotyping of 4 single nucleotide polymorphisms in the catechol-o-methyltransferase (COMT) gene was performed using giant magnetoresistive biosensors to determine if hypnotizable individuals can be identified for targeted hypnosis referrals. For individuals with the proposed ‘optimal’ COMT diplotypes, 89.5% score highly on the Hypnotic Induction Profile (OR = 6.12, 95%CI = 1.26-28.75), which identified 40.5% of the treatable popula...
Source: Journal of Molecular Diagnostics - January 23, 2023 Category: Pathology Authors: Dana L. Cortade, Jessie Markovits, David Spiegel, Shan X. Wang Tags: Regular Article Source Type: research
Evaluation of the Novaplex II HPV28 Detection Assay for HPV Typing in Formalin-Fixed, Paraffin-Embedded Tissues
Prophylactic human papillomavirus (HPV) vaccines are recommended for prevention of HPV-associated cancers. Type-specific detection of HPV in formalin-fixed, paraffin-embedded (FFPE) tissues retrieved from diagnostic pathology laboratories is important in monitoring the impact of HPV vaccines. However, few typing assays have been validated for testing FFPE samples. Results of the Novaplex II HPV28 Detection (Novaplex) assay were compared with those from the reference assay (Linear Array with reflex Line Probe Assay) on 708 FFPE samples from cervical lesions. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - January 21, 2023 Category: Pathology Authors: Hem R. Thapa, Elizabeth R. Unger, Troy D. Querec Tags: Regular article Source Type: research
Evaluation of the Novaplex II HPV28 Detection Assay for HPV Typing in Formalin-Fixed Paraffin-Embedded Tissues
Prophylactic human papillomavirus (HPV) vaccines are recommended for prevention of HPV-associated cancers. Type-specific detection of HPV in formalin-fixed paraffin-embedded (FFPE) tissues retrieved from diagnostic pathology laboratories is important in monitoring the impact of HPV vaccines. However, few typing assays have been validated for testing FFPE samples. We compared results of the Novaplex II HPV28 Detection (Novaplex) assay with those from our reference assay (Linear Array with reflex Line Probe Assay) on 708 FFPE samples from cervical lesions. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - January 21, 2023 Category: Pathology Authors: Hem R. Thapa, Elizabeth R. Unger, Troy D. Querec Tags: Regular Article Source Type: research
Editorial Board
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - January 20, 2023 Category: Pathology Source Type: research
Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - January 20, 2023 Category: Pathology Source Type: research
