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Diagnosis of challenging spinal muscular atrophy cases with long-read sequencing J. Mol. Diagn. (IF 4.1) Pub Date : 2024-03-13 Ningning Wang, Kexin Jiao, Jin He, Bochen Zhu, Nachuan Cheng, Jian Sun, Lan Chen, Wanjin Chen, Lingyun Gong, Kai Qiao, Jianying Xi, Qihan Wu, Chongbo Zhao, Wenhua Zhu
Spinal Muscular Atrophy (SMA) is an autosomal recessive neuromuscular disorder primarily caused by the deletion or mutation of the Survival Motor Neuron 1 () gene. This study assesses the diagnostic potential of Long-Read Sequencing (LRS) in three SMA patients. For Patient 1, who has a heterozygous deletion, LRS unveiled a missense mutation in exon 5. In Patient 2, an -mediated rearrangement covering
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Assay Validation of Cell-Free DNA Shallow Whole Genome Sequencing To Determine Tumor Fraction in Advanced Cancers J. Mol. Diagn. (IF 4.1) Pub Date : 2024-03-13 Micah Rickles-Young, Gabriel Tinoco, Junko Tsuji, Sam Pollock, Marcy Haynam, Heather Lefebvre, Kristyn Glover, Dwight H. Owen, Katharine A. Collier, Gavin Ha, Viktor A. Adalsteinsson, Carrie Cibulskis, Niall J. Lennon, Daniel G. Stover
Blood-based ‘liquid biopsy’ is increasingly utilized in clinical care of cancer patients and fraction of tumor-derived DNA in circulation (‘tumor fraction’, TFx) has demonstrated clinical validity across multiple cancer types. To determine TFx, shallow whole genome sequencing of cell-free DNA can be performed from a single blood sample, using an established computational pipeline (ichorCNA), without
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Optical Genome Mapping for Comprehensive Cytogenetic Analysis of Soft-Tissue and Bone Tumors for Diagnostic Purposes J. Mol. Diagn. (IF 4.1) Pub Date : 2024-02-22 Jef Baelen, Barbara Dewaele, Maria Debiec-Rychter, Raphael Sciot, Patrick Schöffski, Daphne Hompes, Friedl Sinnaeve, Hazem Wafa, Isabelle Vanden Bempt
Soft-tissue and bone tumors represent a heterogeneous group of tumors encompassing more than 100 histologic subtypes today. Identifying genetic aberrations increasingly is important in these tumors for accurate diagnosis. Although gene mutations typically are detected by second-generation sequencing, the identification of structural variants (SVs) and copy number alterations (CNAs) remains challenging
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Machine Learning–Supported Diagnosis of Small Blue Round Cell Sarcomas Using Targeted RNA Sequencing J. Mol. Diagn. (IF 4.1) Pub Date : 2024-02-21 Lea Dewi Schlieben, Maria Giulia Carta, Evgeny A. Moskalev, Robert Stöhr, Markus Metzler, Manuel Besendörfer, Norbert Meidenbauer, Sabine Semrau, Rolf Janka, Robert Grützmann, Stefan Wiemann, Arndt Hartmann, Abbas Agaimy, Florian Haller, Fulvia Ferrazzi
Small blue round cell sarcomas (SBRCSs) are a heterogeneous group of tumors with overlapping morphologic features but markedly varying prognosis. They are characterized by distinct chromosomal alterations, particularly rearrangements leading to gene fusions, whose detection currently represents the most reliable diagnostic marker. Ewing sarcomas are the most common SBRCSs, defined by gene fusions involving
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Universal Digital High-Resolution Melt Analysis for the Diagnosis of Bacteremia J. Mol. Diagn. (IF 4.1) Pub Date : 2024-02-21 April Aralar, Tyler Goshia, Nanda Ramchandar, Shelley M. Lawrence, Aparajita Karmakar, Ankit Sharma, Mridu Sinha, David T. Pride, Peiting Kuo, Khrissa Lecrone, Megan Chiu, Karen Mestan, Eniko Sajti, Michelle Vanderpool, Sarah Lazar, Melanie Crabtree, Yordanos Tesfai, Stephanie I. Fraley
Fast and accurate diagnosis of bloodstream infection is necessary to inform treatment decisions for septic patients, who face hourly increases in mortality risk. Blood culture remains the gold standard test but typically requires ∼15 hours to detect the presence of a pathogen. Here, the potential for universal digital high-resolution melt (U-dHRM) analysis to accomplish faster broad-based bacterial
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Microarray-Based DNA Methylation Profiling: Validation Considerations for Clinical Testing J. Mol. Diagn. (IF 4.1) Pub Date : 2024-02-18 Marco L. Leung, Zied Abdullaev, Lucas Santana-Santos, John M. Skaugen, Stephen Moore, Jianling Ji
Microarray-based methylation profiling has emerged as a valuable tool for refining diagnoses and revealing novel tumor subtypes, particularly in central nervous system tumors. Despite the increasing adoption of this technique in clinical genomic laboratories, no technical standards have been published in establishing minimum criteria for test validation. A working group with experience and expertise
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Analytical Validation of a 37-Gene Next-Generation Sequencing Panel for Myeloid Malignancies and Review of Initial Findings, including Reclassification of Acute Myeloid Leukemias and Myelodysplastic Syndromes Using the 2022 World Health Organization/International Consensus Classification/European LeukemiaNet Guidelines J. Mol. Diagn. (IF 4.1) Pub Date : 2024-02-15 Becky Leung, Hnin Aung, Adayapalam Nandini, Ghusoon Abdulrasool, Chiyan Lau, Louise Seymour
Myeloid neoplasms are clonal disorders that arise via acquisition of genetic mutations leading to excessive proliferation and defective differentiation. Mutational profiling is vital as it has implications on diagnosis, prognosis, and therapeutic decision making. Next generation sequencing (NGS) has become a mainstay in the evaluation of myeloid malignancies, as it enables efficient characterisation
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Enhancing Trypanosomatid Identification and Genotyping with Oxford Nanopore Sequencing J. Mol. Diagn. (IF 4.1) Pub Date : 2024-02-13 Lissa Cruz-Saavedra, Carlos Ospina, Luz Helena Patiño, Juan Carlos Villar, Luis David Sáenz Pérez, Omar Cantillo-Barraza, Jeiczon Jaimes-Dueñez, Nathalia Ballesteros, Tatiana Cáceres, Gustavo Vallejo, Juan David Ramírez
Trypanosomatids, including and species, present significant medical and veterinary challenges causing substantial economic losses, health complications, and even fatalities. Diagnosing and genotyping these species and their genotypes is often complex, involving multiple steps. This study aimed to develop an amplicon-based sequencing (ABS) method utilizing Oxford Nanopore long-read sequencing to enhance
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Comprehensive Genomic Analysis Identifies a Diverse Landscape of Sideroblastic and Nonsideroblastic Iron-Related Anemias with Novel and Pathogenic Variants in an Iron-Deficient Endemic Setting J. Mol. Diagn. (IF 4.1) Pub Date : 2024-02-13 Pankaj Sharma, Prateek Bhatia, Minu Singh, Manu Jamwal, Swetha Pallavelangini, Reena Das, Pankaj Malhotra, Savita Verma Attri, Sarah Ducamp, Mark D. Fleming, Amita Trehan
Inherited iron metabolism defects are possibly missed or underdiagnosed in iron-deficient endemic settings due to a lack of awareness or a methodical screening approach. Hence, we planned a systematic evaluation of anemia cases (2019-2021) based on clinical phenotype, normal screening tests (HPLC, alpha gene sequencing, ESR, CRP, tTG), and abnormal iron profile by targeted NGS (26 gene-panel) supplemented
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Significance Associated with Phenotype (SAP) Score Aids in Variant Prioritization for Exome Sequencing Analysis J. Mol. Diagn. (IF 4.1) Pub Date : 2024-02-13 Brian Lee, Lily Nasanovsky, Lishuang Shen, Dennis T. Maglinte, Yachen Pan, Xiaowu Gai, Ryan J. Schmidt, Gordana Raca, Jaclyn A. Biegel, Megan Roytman, Paul An, Carol J. Saunders, Emily G. Farrow, Soheil Shams, Jianling Ji
Several annotation-based methods have been developed to prioritize variants in exome sequencing analysis. This study introduces a novel metric, the Significance Associated with Phenotypes (SAP) score, which generates a statistical score by comparing an individual's observed phenotypes against existing gene-phenotype associations. To evaluate the SAP score, a retrospective analysis was performed on
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Extraction of Cell-Free DNA J. Mol. Diagn. (IF 4.1) Pub Date : 2024-02-02 Simone Karlsson Terp, Inge Søkilde Pedersen, Malene Pontoppidan Stoico
Cell-free DNA (cfDNA) serves as a valuable biomarker for early disease detection and monitoring. However, the use of cfDNA for analysis faces challenges owing to general low but variable abundance and fragmentation. Preanalytical factors, including cfDNA extraction, impact cfDNA quality and quantity. Efficient and robust cfDNA extraction is essential for reliable results in downstream applications
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Engraftment and Measurable Residual Disease Monitoring after Hematopoietic Stem Cell Transplantation J. Mol. Diagn. (IF 4.1) Pub Date : 2024-02-02 Aiwen Zhang, Stacey Macecevic, Dawn Thomas, Jeffrey Allen, Sarah Mandley, Paul Kawczak, Raymond Jurcago, Jennifer Tyler, Heather Casey, David Bosler, Ronald Sobecks, Betty Hamilton, Craig Sauter, Shin Mineishi, David Claxton, Hiroko Shike
Chimerism testing supports the study of engraftment and measurable residual disease (MRD) in patients after allogeneic hematopoietic stem cell transplant. In chimerism MRD, relapse can be predicted by increasing mixed chimerism of recipient allele (Δ) ≥0.1% in peripheral blood, proliferating recipient cells as a surrogate of tumor activity. Conventionally, the combination of two chimerism methods,
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Enhancing the Reliability of PMP22 Copy Number Variation Detection with an Inherited Peripheral Neuropathy Panel J. Mol. Diagn. (IF 4.1) Pub Date : 2024-02-01 Jong Kwon Lee, Hyemi Kwon, Jong-Ho Park, Mi-Ae Jang, Young-gon Kim, Jong-Won Kim, Byung-Ok Choi, Ja-Hyun Jang
The utility of the next-generation sequencing (NGS) panel could be increased in hereditary peripheral neuropathies, given that the duplication of PMP22 is a major abnormality. In the present study, the analytical performance of an algorithm for detecting PMP22 copy number variation (CNV) from the NGS panel data was evaluated. The NGS panel covers 141 genes, including PMP22 and five genes within 1.5-Mb
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Next-Generation Sequencing Trends among Adult Patients with Select Advanced Tumor Types J. Mol. Diagn. (IF 4.1) Pub Date : 2024-02-01 Andrea Ferreira-Gonzalez, Brian Hocum, Gilbert Ko, Sohul Shuvo, Sreevalsa Appukkuttan, Svetlana Babajanyan
There are limited data on the prevalence of next-generation sequencing (NGS) in the United States, especially in light of the increasing importance of identifying actionable oncogenic variants due to molecular biomarker-based therapy approvals. This retrospective study of adult patients with select metastatic solid tumors and central nervous system tumors from the Optum Clinformatics Data Mart US health
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The Clinical Validity of Urinary Pellet DNA Monitoring for the Diagnosis of Recurrent Bladder Cancer J. Mol. Diagn. (IF 4.1) Pub Date : 2024-02-01 Masakazu Abe, Hayato Hiraki, Takashi Tsuyukubo, Sadahide Ono, Shigekatsu Maekawa, Daichi Tamura, Akiko Yashima-Abo, Renpei Kato, Hiromitsu Fujisawa, Takeshi Iwaya, Woong-Yang Park, Masashi Idogawa, Takashi Tokino, Wataru Obara, Satoshi S. Nishizuka
The aim of this study is to evaluate the clinical validity of monitoring urine pellet DNA (upDNA) of bladder cancer (BC) by digital PCR (dPCR) as a biomarker for early recurrence prediction, treatment efficacy evaluation, and no-recurrence corroboration. Tumor panel sequencing was first performed to select patient-unique somatic mutations to monitor both upDNA and circulating tumor DNA (ctDNA) by dPCR
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Defining an optimized workflow for enriching and analyzing residual tumor populations using intracellular markers. J. Mol. Diagn. (IF 4.1) Pub Date : 2024-01-26 Eve Marie Coulter, Findlay Bewicke-Copley, Maximilian Mossner, Trevor Graham, Jude Fitzgibbon, Jessica Okosun
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Identification of synonymous pathogenic variants in monogenic disorders by integrating exome with transcriptome sequencing J. Mol. Diagn. (IF 4.1) Pub Date : 2024-01-26 Lin Zhang, Haijuan Lou, Yanhong Huang, Liping Dong, Xueye Gong, Xiaoning Zhang, Wenqi Bao, Rui Xiao
Exome sequencing (ES) is becoming a first-tier clinical diagnostic test for Mendelian diseases, drastically reducing the time and cost of diagnostic odyssey and improving the diagnosis rate. Despite its success, ES faces practical challenges in assessing the pathogenicity of numerous intronic and synonymous variants, leaving a significant proportion of patients undiagnosed. In this study, a whole blood
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Somatic genomic and transcriptomic characterization of primary ovarian serous borderline tumors and low-grade serous carcinomas. J. Mol. Diagn. (IF 4.1) Pub Date : 2024-01-26 Ivana Stružinská, Nikola Hájková, Jan Hojný, Eva Krkavcová, Romana Michálková, Quang Hiep Bui, Radoslav Matěj, Jan Laco, Jana Drozenová, Pavel Fabian, Petr Škapa, Zuzana Špůrková, David Cibula, Filip Frühauf, Tomáš Jirásek, Tomáš Zima, Gábor Méhes, Michaela Kendall Bártů, Kristýna Němejcová, Pavel Dundr
Low-grade serous carcinomas (LGSC) probably develop from serous borderline tumors (SBT), where the micropapillary type (mSBT) has the highest risk of progression. The sensitivity of LGSC to standard chemotherapy is limited, so alternative therapeutic approaches are needed, including targeted treatment. However, current knowledge about molecular landscape of LGSC and mSBT is limited. A sample set of
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2024 Updates to American Medical Association’s Current Procedural Terminology Codes for Oncology Panel Testing J. Mol. Diagn. (IF 4.1) Pub Date : 2024-01-25 Victoria M. Pratt
Abstract not available
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Detection of Constitutional Structural Variants by Optical Genome Mapping: A Multisite Study of Postnatal Samples J. Mol. Diagn. (IF 4.1) Pub Date : 2024-01-09 Ulrich Broeckel, M. Anwar Iqbal, Brynn Levy, Nikhil Sahajpal, Peter L. Nagy, Gunter Scharer, Vanessa Rodriguez, Aaron Bossler, Aaron Stence, Cindy Skinner, Steven A. Skinner, Ravindra Kolhe, Roger Stevenson
Optical genome mapping is a high-resolution technology that can detect all types of structural variations in the genome. This second phase of a multisite study compares the performance of optical genome mapping and current standard-of-care methods for diagnostic testing of individuals with constitutional disorders, including neurodevelopmental impairments and congenital anomalies. Among the 627 analyses
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Prenatal testing for variants in genes associated with hereditary cancer risk: laboratory experience and considerations J. Mol. Diagn. (IF 4.1) Pub Date : 2024-01-01 Lynne S. Rosenblum, Stephanie M. Auger, Hui Zhu, Zhaoqing Zhou, Winnie Xin, Jennifer Reiner, Zena Wolf, Natalia T. Leach
Prenatal molecular genetic testing for familial variants that cause inherited disorders has been performed for decades and is accepted as standard of care. However, the spectrum of genes considered for prenatal testing is expanding due to genetic testing for hereditary cancer risk (HCR) and inclusion of conditions with associated cancer risk in carrier screening panels. A few of these disorders, such
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Comparing the Diagnostic Performance of qPCR, ddPCR, and NGS Liquid Biopsies for HPV-Associated Cancers J. Mol. Diagn. (IF 4.1) Pub Date : 2023-12-15 Saskia Naegele, Daniel A. Ruiz-Torres, Yan Zhao, Deborah Goss, Daniel L. Faden
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
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Uncovering the Genetic Etiology of Inherited Bone Marrow Failure Syndromes Using a Custom-designed Next Generation Sequencing Panel J. Mol. Diagn. (IF 4.1) Pub Date : 2023-12-14 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, Kristin Zelley, Suzanne MacFarland, Peter Kurre, Timothy S. Olson, Marilyn M. Li
Inherited bone marrow failure syndromes (IBMFS) are a group of heterogeneous disorders that account for approximately 30% of pediatric bone marrow failure cases and are often associated with developmental abnormalities and cancer predisposition. 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
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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 J. Mol. Diagn. (IF 4.1) Pub Date : 2023-12-14 Jeffrey A. SoRelle, Birgit H. Funke, Celeste C. Eno, Jianling Ji, Avni Santani, Pinar Bayrak-Toydemir, Megan Wachsmann, Karen E. Wain, Rong Mao
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
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Quantification of Measurable Residual Disease Detection by Next Generation Sequencing-based Clonality Testing in B-cell and Plasma Cell Neoplasms J. Mol. Diagn. (IF 4.1) Pub Date : 2023-12-14 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 Roshal, Khedoudja Nafa, Maria E. Arcila
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
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Operationalizing Quality Assurance for Clinical Illumina Somatic Next-Generation Sequencing Pipelines J. Mol. Diagn. (IF 4.1) Pub Date : 2023-12-10 Joshua Bridgers, Kenyon Alexander, Aly Karsan
Quality assurance (QA) is essential for precision oncology workflows, in particular in the clinical setting. However, because of numerous variations in laboratory and bioinformatics pipelines, QA practices remain non-standardized, are often ad hoc, and are lacking longitudinal tracking. A selected review of existing software was performed for quality control of Illumina next-generation sequencing data
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MLH1 Promotor Hypermethylation in Colorectal and Endometrial Carcinomas from Patients with Lynch Syndrome J. Mol. Diagn. (IF 4.1) Pub Date : 2023-12-05 Noah C. Helderman, Katarina D. Andini, Monique E. van Leerdam, Liselotte P. van Hest, Daniël 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 T.H.B.M. Smit, Diantha Terlouw, Tom van Wezel, Hans Morreau, Maartje Nielsen
Screening for Lynch syndrome (LS) in colorectal cancer (CRC) and endometrial cancer 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 the constitutional MLH1 variants from somatic epimutations. Recently, multiple studies have reported that
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Droplet Digital PCR for Fast and Accurate Characterization of NF1 Locus Deletions: Confirmation of the Predominant Maternal Origin of Type-1 Deletions J. Mol. Diagn. (IF 4.1) Pub Date : 2023-11-25 Laurence Pacot, Manuela Ye, Juliette Nectoux, Ingrid Laurendeau, Audrey Briand-Suleau, Audrey Coustier, Théodora Maillard, Cécile Barbance, Lucie Orhant, Nicolas Vaucouleur, Hélène Blanché, Béatrice Parfait, Pierre Wolkenstein, Michel Vidaud
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
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Variant Classification Discordance: Contributing Factors and Predictive Models J. Mol. Diagn. (IF 4.1) Pub Date : 2023-11-24 Hamid Ghaedi, Scott K. Davey, Harriet Feilotter
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. The current study used ClinVar data to identify characteristics that would make variants more likely to be associated with
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Cost-Effective Cas9-Mediated Targeted Sequencing of Spinocerebellar Ataxia Repeat Expansions J. Mol. Diagn. (IF 4.1) Pub Date : 2023-11-24 Keiji Tachikawa, Takahiro Shimizu, Takeshi Imai, Riyoko Ko, Yosuke Kawai, Yosuke Omae, Katsushi Tokunaga, Martin C. Frith, Yoshihisa Yamano, Satomi Mitsuhashi
Hereditary repeat diseases are caused by an abnormal expansion of short tandem repeats in the genome. Among them, spinocerebellar ataxia (SCA) is a heterogeneous disease, and currently, 16 responsible repeats are known. Genetic diagnosis is obtained by analyzing the number of repeats through separate testing of each repeat. Although simultaneous detection of candidate repeats using current massively
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FindDNAFusion: An Analytical Pipeline with Multiple Software Tools Improves Detection of Cancer-Associated Gene Fusions from Genomic DNA J. Mol. Diagn. (IF 4.1) Pub Date : 2023-11-24 Xiaokang Pan, Huolin Tu, Nehad Mohamed, Matthew Avenarius, Sean Caruthers, Weiqiang Zhao, Dan Jones
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
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An Exome Capture-Based RNA-Sequencing Assay for Genome-Wide Identification and Prioritization of Clinically Important Fusions in Pediatric Tumors J. Mol. Diagn. (IF 4.1) Pub Date : 2023-11-24 Jonathan Buckley, Ryan J. 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 Gai, Jaclyn A. Biegel
This study reports 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 used 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
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Clinical Utility and Reimbursement of Next-Generation Sequencing–Based Testing for Myeloid Malignancies J. Mol. Diagn. (IF 4.1) Pub Date : 2023-11-20 Craig R. Soderquist, Christopher Freeman, Wen-Hsuan Lin, Rebecca J. Leeman-Neill, Yue Gu, Melissa C. Carter, Kate C. Stutzel, Evelyn Sigcha, Bachir Alobeid, Helen Fernandes, Govind Bhagat, Mahesh M. Mansukhani, Susan J. Hsiao
Next-generation sequencing is becoming increasingly important for the diagnosis, risk stratification, and management of patients with established or suspected myeloid malignancies. These tests are being incorporated into clinical practice guidelines and many genetic alterations now constitute disease classification criteria. However, the reimbursement for these tests is uncertain. This study analyzed
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Transcriptome Sequencing Allows Comprehensive Genomic Characterization of Pediatric B-Acute Lymphoblastic Leukemia in an Academic Clinical Laboratory J. Mol. Diagn. (IF 4.1) Pub Date : 2023-11-18 Zunsong Hu, Alexandra E. Kovach, Venkata Yellapantula, Dejerianne Ostrow, Andrew Doan, Jianling Ji, Ryan J. Schmidt, Zhaohui Gu, Deepa Bhojwani, Gordana Raca
Studies have shown the power of transcriptome sequencing [RNA sequencing (RNA-Seq)] in identifying known and novel oncogenic drivers and molecular subtypes of B-acute lymphoblastic leukemia (B-ALL). The current study investigated whether the clinically validated RNA-Seq assay, coupled with a custom analysis pipeline, could be used for a comprehensive B-ALL classification. Following comprehensive clinical
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Pan-Tumor Analytical Validation and Osimertinib Clinical Validation in EGFR Mutant Non–Small-Cell Lung Cancer, Supporting the First Next-Generation Sequencing Liquid Biopsy in Vitro Diagnostic J. Mol. Diagn. (IF 4.1) Pub Date : 2023-11-18 Jhanelle E. Gray, Ji-Youn Han, Aino Telaranta-Keerie, Xiangning Huang, Alexander Kohlmann, Rachel Hodge, Yuri Rukazenkov, Juliann Chmielecki, Carin R. Espenschied, Martina Lefterova, Yi-Long Wu, Suresh S. Ramalingam, J. Carl Barrett, Justin I. Odegaard
Comprehensive genotyping is necessary to identify therapy options for patients with advanced cancer; however, many cancers are not tested, partly because of tissue limitations. Next-generation sequencing (NGS) liquid biopsies overcome some limitations, but clinical validity is not established and adoption is limited. Herein, clinical bridging studies used pretreatment plasma samples and data from FLAURA
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Toward a Comprehensive One-Stop Shop for Somatic Genomic Profiling in Childhood Acute Lymphoblastic Leukemia J. Mol. Diagn. (IF 4.1) Pub Date : 2023-11-14 Shawn H.R. Lee
Abstract not available
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Spotlight on Spotlight: The Newest Submission Category from The Journal of Molecular Diagnostics J. Mol. Diagn. (IF 4.1) Pub Date : 2023-11-11 Ronald M. Przygodzki
Abstract not available
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The Power of the Association for Molecular Pathology Is Its People: A Reflection on a Fulfilling Career with an Exceptional Society J. Mol. Diagn. (IF 4.1) Pub Date : 2023-10-27 Mary Steele Williams
Abstract not available
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Analytical Validation of an Automated Semiconductor-Based Next-Generation Sequencing Assay for Detection of DNA and RNA Alterations in Myeloid Neoplasms J. Mol. Diagn. (IF 4.1) Pub Date : 2023-10-23 Nora Zbieranski, Giovanni Insuasti-Beltran
Myeloid neoplasms are heterogeneous tumors derived from early hematopoietic progenitors. Most international guidelines, including the European LeukemiaNet 2022 update, recommend testing a comprehensive set of genes, most within a 3- to 5-day period for optimal treatment decisions. Next-generation sequencing gene panels are essential for identifying genetic alterations, risk stratification, and determining
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Analytical Performance Evaluation of a 523-Gene Circulating Tumor DNA Assay for Next-Generation Sequencing–Based Comprehensive Tumor Profiling in Liquid Biopsy Samples J. Mol. Diagn. (IF 4.1) Pub Date : 2023-10-20 Johannes Harter, Eleonora Buth, Janina Johaenning, Florian Battke, Maria Kopp, Henning Zelba, Martin Schulze, Jiri Koedding, Saskia Biskup
Next-generation sequencing (NGS)–based comprehensive tumor profiling from liquid biopsy samples can significantly improve diagnosis and monitoring of tumors when high-quality tissue material is difficult to obtain. In addition, it offers the potential to capture the entire complexity of the tumor, which is particularly important for highly heterogeneous or metastatic tumors. Here, we report the findings
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miR-122 and miR-21 are Stable Components of miRNA Signatures of Early Lung Cancer after Validation in Three Independent Cohorts J. Mol. Diagn. (IF 4.1) Pub Date : 2023-10-20 Joanna Zyla, Rafal Dziadziuszko, Michal Marczyk, Magdalena Sitkiewicz, Magdalena Szczepanowska, Edoardo Bottoni, Giulia Veronesi, Witold Rzyman, Joanna Polanska, Piotr Widlak
Several panels of circulating miRNAs have been reported as potential biomarkers of early lung cancer, yet the overlap of components between different panels is limited, and the universality of proposed biomarkers has been minimal across proposed panels. To assess the stability of the diagnostic potential of plasma miRNA signature of early lung cancer among different cohorts, a panel of 24 miRNAs tested
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Clinical Accuracy of Alinity m HR HPV Assay on Self- versus Clinician-Taken Samples Using the VALHUDES Protocol J. Mol. Diagn. (IF 4.1) Pub Date : 2023-10-20 Ardashel Latsuzbaia, Severien Van Keer, Davy Vanden Broeck, Steven Weyers, Gilbert Donders, Philippe De Sutter, Wiebren Tjalma, Jean Doyen, Alex Vorsters, Marc Arbyn
The VALHUDES protocol was established to evaluate clinical accuracy of human papillomavirus (HPV) assays to detect cervical precancer on first-void urine (FVU) and vaginal self-samples versus matched clinician-collected cervical samples (CCSs). Here we evaluated clinical performance of Alinity m HR HPV assay in a colposcopy referral population. Home-collected FVU (Colli-Pee FV 5020) 1 day before colposcopy
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A New Set of in Silico Tools to Support the Interpretation of ATM Missense Variants Using Graphical Analysis J. Mol. Diagn. (IF 4.1) Pub Date : 2023-10-19 Luz-Marina Porras, Natàlia Padilla, Alejandro Moles-Fernández, Lidia Feliubadaló, Marta Santamariña-Pena, Alysson T. Sánchez, Anael López-Novo, Ana Blanco, Miguel de la Hoya, Ignacio J. Molina, Ana Osorio, Marta Pineda, Daniel Rueda, Clara Ruiz-Ponte, Ana Vega, Conxi Lázaro, Orland Díez, Sara Gutiérrez-Enríquez, Xavier de la Cruz
Establishing the pathogenic nature of variants in ATM, a gene associated with breast cancer and other hereditary cancers, is crucial for providing patients with adequate care. Unfortunately, achieving good variant classification is still difficult. To address this challenge, we extended the range of in silico tools with a series of graphical tools devised for the analysis of computational evidence
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Production and Performance Assessment of a Severe Acute Respiratory Syndrome Coronavirus 2 Biomimetic in a Verification Program for Pandemic Readiness J. Mol. Diagn. (IF 4.1) Pub Date : 2023-10-18 Edith E. Machowski, Anna E. Reyneke, Dean E. Sher, Bavesh D. Kana
During the early stages of the 2019 coronavirus disease (COVID-19) pandemic in South Africa, one of many challenges included availability of control material for laboratory proficiency testing programs. Proficiency testing control material using live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or RNA extracted from cell culture was either biohazardous or costly, particularly in resource-limited