Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - May 17, 2023 Category: Pathology Source Type: research
Recommendations for Next-Generation Sequencing Germline Variant Confirmation
Clinical laboratory implementation of next-generation sequencing (NGS) –based constitutional genetic testing has been rapid and widespread. In the absence of widely adopted comprehensive guidance, there remains substantial variability among laboratories in the practice of NGS. One issue of sustained discussion in the field is whether and to what extent orthogonal con firmation of genetic variants identified by NGS are necessary or helpful. The Association for Molecular Pathology Clinical Practice Committee convened the NGS Germline Variant Confirmation Working Group to assess current evidence regarding orthogonal confirm...
Source: Journal of Molecular Diagnostics - May 17, 2023 Category: Pathology Authors: Kristy R. Crooks, Kelly D. Farwell Hagman, Diana Mandelker, Avni Santani, Ryan J. Schmidt, Robyn L. Temple-Smolkin, Stephen E. Lincoln Tags: Special article Source Type: research
Recommendations for Next-Generation Sequencing Germline Variant Confirmation: A Joint Report of the Association for Molecular Pathology and National Society of Genetic Counselors
Clinical laboratory implementation of next-generation sequencing (NGS)-based constitutional genetic testing has been rapid and widespread. In the absence of widely adopted comprehensive guidance, there remains substantial variability among laboratories in the practice of NGS. One issue of sustained discussion in the field is whether and to what extent orthogonal confirmation of genetic variants identified by NGS is necessary or helpful. The Association for Molecular Pathology Clinical Practice Committee convened the NGS Germline Variant Confirmation Working Group to assess current evidence regarding orthogonal confirmation...
Source: Journal of Molecular Diagnostics - May 17, 2023 Category: Pathology Authors: Kristy R. Crooks, Kelly D. Farwell Hagman, Diana Mandelker, Avni Santani, Ryan J. Schmidt, Robyn L. Temple-Smolkin, Stephen E. Lincoln Tags: Special Article Source Type: research
RNA Sequencing Identifies Novel NRG1 Fusions in Solid Tumors that Lack Co-Occurring Oncogenic Drivers
NRG1 gene fusions are rare, therapeutically relevant, oncogenic drivers that occur across solid tumor types. To understand the landscape of NRG1 gene fusions, 4397 solid tumor formalin-fixed, paraffin-embedded samples consecutively tested by comprehensive genomic and immune profiling during standard care were analyzed. Nineteen NRG1 fusions were found in 17 unique patients, across multiple tumor types, including non –small-cell lung (n = 7), breast (n = 2), colorectal (n = 3), esophageal (n = 2), ovarian (n = 1), pancreatic (n = 1), and unknown primary (n = 1) carcinomas, with a cumulative incidence of 0.38...
Source: Journal of Molecular Diagnostics - May 8, 2023 Category: Pathology Authors: Eric Severson, B.R. Achyut, Mary Nesline, Sarabjot Pabla, Rebecca A. Previs, Geoffrey Kannan, Anjen Chenn, Shengle Zhang, Roger Klein, Jeffrey Conroy, Mark Sausen, Pratheesh Sathyan, Kamal S. Saini, Aradhana Ghosh, Taylor J. Jensen, Prasanth Reddy, Shakti Tags: Regular article Source Type: research
RNA sequencing identifies novel NRG1-fusions in solid tumors that lack co-occurring oncogenic drivers
NRG1 gene fusions are rare, therapeutically relevant, oncogenic drivers that occur across solid tumor types. To understand the landscape of NRG1 gene fusions, 4,397 solid tumor FFPE samples consecutively tested by comprehensive genomic and immune profiling during standard care were analyzed. Nineteen (19) NRG1 fusions were found in 17 unique patients, across multiple tumor types including non-small cell lung (n=7), breast (n=2), colorectal (n=3), esophageal (n=2), ovarian (n=1), pancreatic (n=1), and unknown primary (n=1) carcinomas, with a cumulative incidence of 0.38%. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - May 8, 2023 Category: Pathology Authors: Eric Severson, B.R. Achyut, Mary Nesline, Sarabjot Pabla, Rebecca A. Previs, Geoffrey Kannan, Anjen Chenn, Shengle Zhang, Roger Klein, Jeffrey Conroy, Mark Sausen, Pratheesh Sathyan, Kamal S. Saini, Aradhana Ghosh, Taylor J. Jensen, Prasanth Reddy, Shakti Tags: Regular Article Source Type: research
Correction
The authors of the article entitled, “Improved Diagnosis of Rare Disease Patients through Systematic Detection of Runs of Homozygosity” (Volume 22, pages 1205–1215 of the September 2020 issue of The Journal of Molecular Diagnostics; DOI: https://doi.org/10.1016/j.jmoldx.2020.06.008) have discovered an omission in the published A cknowledgments. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - May 1, 2023 Category: Pathology Tags: Correction Source Type: research
Editorial Board
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - May 1, 2023 Category: Pathology Source Type: research
Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - May 1, 2023 Category: Pathology Source Type: research
Highly Selective, Single-Tube Colorimetric Assay for Detection of Multiple Mutations in the Epidermal Growth Factor Receptor Gene
Many closed-tube methods are designed to detect DNA biomarkers. However, the utility of biomarkers such as a DNA mutation related to personalized medicine is limited as the operation of expensive detection instruments requires well-trained technicians. Therefore, we developed a simple and cheap colorimetric assay based on aggregation of silica-gold nanoparticle-modified probes, with linking probes, to detect mutations. This method consists of target amplification, sequence identification, and aggregation of the silica-gold nanoparticle –modified probes. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - May 1, 2023 Category: Pathology Authors: Jianping Wang, Tengfei Pan, Song Zhang Tags: Technical advance Source Type: research
Next-Generation Sequencing –Based Genomic Profiling of Children with Acute Myeloid Leukemia
Pediatric acute myeloid leukemia (AML) represents a major cause of childhood leukemic mortality, with only a limited number of studies investigating the molecular landscape of the disease. Here, we present an integrative analysis of cytogenetic and molecular profiles of 75 patients with pediatric AML from a multicentric, real-world patient cohort treated according to AML BFM protocols. Targeted next-generation sequencing of 54 genes revealed 17 genes that were recurrently mutated in>5% of patients. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - April 21, 2023 Category: Pathology Authors: Szilvia Krizs án, Borbála Péterffy, Bálint Egyed, Tibor Nagy, Endre Sebestyén, Lajos László Hegyi, Zsuzsanna Jakab, Dániel J. Erdélyi, Judit Müller, György Péter, Krisztina Csanádi, Krisztián Kállay, Gergely Kriván, Gábor Barna, Gábor Be Tags: Regular article Source Type: research
In Silico Approaches to Proficiency Testing
Next-generation sequencing (NGS) has become a ubiquitous method for clinical molecular testing. Advantages of NGS include high-throughput sequencing, low cost per base, flexible workflows, suitability for multiplexing, and regulatory approval of certain platforms. Clinical laboratories engage in continuous monitoring and quality improvement, both for development and validation of their tests and as a condition of accreditation. External quality assessments through proficiency testing (PT) programs promote excellence in clinical testing. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - April 21, 2023 Category: Pathology Authors: Ian S. Hagemann, Ahmet Zehir, Carlos J. Suarez, Larissa V. Furtado, Jaimie Halley, Megan Kane, Nicole Mot, Patricia Vasalos, Joel T. Moncur, Eric Q. Konnick Tags: Guest editorial Source Type: research
Real-Time, Multiplexed SHERLOCK for in Vitro Diagnostics
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the need for simple, low-cost, and scalable diagnostics that can be widely deployed for rapid testing. Clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostics have emerged as a promising technology, but its implementation in clinical laboratories has been limited by the requirement of a separate amplification step prior to CRISPR-associated (Cas) enzyme –based detection. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - April 21, 2023 Category: Pathology Authors: Jennifer M. Pena, Brendan J. Manning, Xiang Li, Elizabeth S. Fiore, Leah Carlson, Kristen Shytle, Peter P. Nguyen, Ishara Azmi, Alex Larsen, Mary K. Wilson, Subha Singh, Marisa C. DeMeo, Pradeep Ramesh, Heike Boisvert, William J. Blake Tags: Regular article Source Type: research
Detecting low-variant allele frequency mosaic pathogenic variants of NF1, TSC2, and AKT3 genes from blood in patients with neurodevelopmental disorders
Growing evidence indicates that early, and late postzygotic mosaicism can cause neurodevelopmental disorders (NDD), but detection of low variant allele frequency (VAF) mosaic variants from blood remains a challenge. We reviewed data of 2,162 patients with NDDs who underwent conventional genetic tests and performed a deep sequencing using specifically designed mosaic NGS panel in the patients with negative genetic test results. Forty-four patents with neurocutaneous syndrome, malformation of cortical development or nonlesional epileptic encephalopathies were included. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - April 21, 2023 Category: Pathology Authors: Se Hee Kim, Soon Sung Kwon, Mi Ri Park, Hyeon Ah Lee, Ji Hun Kim, JiHoon Cha, Sangwoo Kim, Seung Tae Baek, Se Hoon Kim, Joon Soo Lee, Heung Dong Kim, Jong Rak Choi, Seung-Tae Lee, Hoon-Chul Kang Tags: Regular Article Source Type: research
Next-generation sequencing-based genomic profiling of children with acute myeloid leukemia
Pediatric acute myeloid leukemia (AML) represents a major cause of childhood leukemic mortality with only a limited number of studies investigating the molecular landscape of the disease. Here, we present an integrative analysis of cytogenetic and molecular profiles of 75 patients with pediatric AML from a multicentric, real-world patient cohort treated according to AML BFM protocols. Targeted next-generation sequencing (NGS) of 54 genes revealed 17 genes that were recurrently mutated in more than 5% of patients. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - April 21, 2023 Category: Pathology Authors: Szilvia Krizs án, Borbála Péterffy, Bálint Egyed, Tibor Nagy, Endre Sebestyén, Lajos László Hegyi, Zsuzsanna Jakab, Dániel J. Erdélyi, Judit Müller, György Péter, Krisztina Csanádi, Krisztián Kállay, Gergely Kriván, Gábor Barna, Gábor Be Tags: Regular Article Source Type: research
Real-time, multiplexed SHERLOCK for in vitro diagnostics
The SARS-CoV-2 pandemic has highlighted the need for simple, low-cost, and scalable diagnostics that can be widely deployed for rapid testing. CRISPR-based diagnostics have emerged as a promising technology, but the implementation in clinical labs has been limited by the requirement of a separate amplification step that occurs prior to Cas enzyme-based detection. Here, we report the discovery of two novel Cas12 enzymes (SLK9 and SLK5-2) that exhibit enzymatic activity at 60 °C, which when combined with LAMP-based isothermal amplification enable a real-time, single step nucleic acid detection method (real-time SHERLOCK). (...
Source: Journal of Molecular Diagnostics - April 21, 2023 Category: Pathology Authors: Jennifer M. Pena, Brendan J. Manning, Xiang Li, Elizabeth S. Fiore, Leah Carlson, Kristen Shytle, Peter P. Nguyen, Ishara Azmi, Alex Larsen, Mary K. Wilson, Subha Singh, Marisa C. DeMeo, Pradeep Ramesh, Heike Boisvert, William J. Blake Tags: Regular Article Source Type: research
