Outlier expression of isoforms by targeted or total RNA sequencing identifies clinically significant genomic variants in hematolymphoid tumors
Recognition of aberrant gene isoforms due to DNA events can impact risk stratification and molecular classification of hematolymphoid tumors. In myelodysplastic syndromes, KMT2A partial tandem duplication (PTD) was one of the top adverse predictors in the International Prognostic Scoring System-Molecular study. In B lymphoblastic leukemia (B-ALL), ERG isoforms have been proposed as markers of favorable-risk DUX4 rearrangements, whereas deletion-mediated IKZF1 isoforms are associated with adverse prognosis and have been extended to the high-risk IKZF1plus signature defined by co-deletions including PAX5. (Source: Journal of...
Source: Journal of Molecular Diagnostics - July 4, 2023 Category: Pathology Authors: Harrison K. Tsai, Tasos Gogakos, Va Lip, Jonathan M. Tsai, Yen-Der Li, Adam S. Fisch, Jonathan Weiss, Weiping Yang, Leslie Grimmett, Daniel DiToro, Eva J. Schaefer, R. Coleman Lindsley, Thai Hoa Tran, Maxime Caron, Sylvie Langlois, Daniel Sinnett, Yana Pi Tags: Regular Article Source Type: research
An Integral Approach to the Molecular Diagnosis of Tuberous Sclerosis Complex
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by the presence of hamartomas in multiple organs. At the molecular level, the disease is caused by pathogenic variants in the TSC1 and TSC2 genes, and only 10% to 25% of clinically diagnosed patients remain negative after multiplex ligation-dependent probe amplification and exon sequencing of both genes. Here, to improve the molecular diagnosis of TSC, we developed an integral approach that includes multiplex ligation-dependent probe amplification and deep-coverage next-generation sequencing of the entire TSC1 and TSC2 genes, along wit...
Source: Journal of Molecular Diagnostics - June 23, 2023 Category: Pathology Authors: Laura Blasco-P érez, Leticia Iranzo-Nuez, Ricard López-Ortega, Desirée Martínez-Cruz, María Camprodon-Gómez, Anna Tenés, María Antolín, Eduardo F. Tizzano, Elena García-Arumí Tags: Regular article Source Type: research
An integral approach to the molecular diagnosis of tuberous sclerosis complex: the role of mosaicism and splicing variants
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by the presence of hamartomas in multiple organs. At the molecular level, the disease is caused by pathogenic variants in the TSC1 and TSC2 genes, and only 10-25% of clinically diagnosed patients remain negative after MLPA and exon sequencing of both genes. Here, to improve the molecular diagnosis of TSC, we developed an integral approach that includes MLPA and deep coverage NGS of the entire TSC1 and TSC2 genes, along with an adapted bioinformatic pipeline to detect variants at low allele frequencies (>1%). (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 23, 2023 Category: Pathology Authors: Laura Blasco-P érez, Leticia Iranzo-Nuez, Ricard López-Ortega, Desirée Martínez-Cruz, María Camprodon-Gómez, Anna Tenés, María Antolín, Eduardo F. Tizzano, Elena García-Arumí Tags: Regular Article Source Type: research
A Novel Microfluidic Dielectrophoresis Technology to Enable Rapid Diagnosis of Mycobacteria tuberculosis in Clinical Samples
To achieve the global efforts to end tuberculosis, affordable diagnostics suitable for true point-of-care implementation are required to reach the missing millions. In addition, diagnostics with increased sensitivity and expanded drug susceptibility testing are needed to address drug resistance and to diagnose low-bacterial burden cases. The laboratory-on-a-chip technology described herein used dielectrophoresis to selectively isolate Mycobacterium tuberculosis from sputum samples, purifying the bacterial population ahead of molecular confirmation by multiplex real-time quantitative PCR. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 22, 2023 Category: Pathology Authors: Catherine M. Moore, Jasvir Dhillon, Rebecca Flynn, Krzysztof Gizynski, Candice Adams, George Morgan, David McGurk, Eduardo Boada, Shireen Shabestary, Jonathan Peat, Jonathan O'Halloran, Neil G. Stoker, Philip D. Butcher, Heather Murton Tags: Regular article Source Type: research
Editorial Board
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 22, 2023 Category: Pathology Source Type: research
Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 22, 2023 Category: Pathology Source Type: research
Comparison of the Clinical Accuracy of Xpert HPV Assay on Vaginal Self-Samples and Cervical Clinician-Taken Samples within the VALHUDES Framework
The accuracy of high-risk human papillomavirus testing with the Xpert HPV assay on vaginal self-samples was compared with clinician-taken samples within the VALHUDES framework. We recruited 523 women in five Belgian colposcopy clinics, of whom 483 (median age, 40 years; interquartile range, 31 to 49 years) were included in the main analysis (226 collected with Evalyn Brush and 257 collected with Qvintip). Cervical samples were collected with Cervex-Brush. Colposcopy and histology outcomes were considered as the reference standard. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 22, 2023 Category: Pathology Authors: Ardashel Latsuzbaia, Davy Vanden Broeck, Severien Van Keer, Steven Weyers, Gilbert Donders, Jean Doyen, Wiebren Tjalma, Philippe De Sutter, Alex Vorsters, Marc Arbyn Tags: Regular article Source Type: research
Characterization of Reference Materials for CYP3A4 and CYP3A5
Pharmacogenetic testing for CYP3A4 is increasingly provided by clinical and research laboratories; however, only a limited number of quality control and reference materials are currently available for many of the CYP3A4 variants included in clinical tests. To address this need, the Division of Laboratory Systems, CDC-based Genetic Testing Reference Material Coordination Program, in collaboration with members of the pharmacogenetic testing and research communities and the Coriell Institute for Medical Research, has characterized 30 DNA samples derived from Coriell cell lines for CYP3A4. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 22, 2023 Category: Pathology Authors: Andrea Gaedigk, Erin C. Boone, Amy J. Turner, Ron H.N. van Schaik, Dilyara Chernova, Wendy Y. Wang, Ulrich Broeckel, Caitlin A. Granfield, Jennell C. Hodge, Reynold C. Ly, Ty C. Lynnes, Matthew W. Mitchell, Ann M. Moyer, Jason Oliva, Lisa V. Kalman Tags: Regular article Source Type: research
Comparison of the clinical accuracy of Xpert HPV on vaginal self- and cervical clinician-taken samples within the VALHUDES framework
The accuracy of hrHPV testing with the Xpert HPV assay on vaginal self-samples was compared with clinician-taken samples within the VALHUDES framework. We recruited 523 women in five Belgian colposcopy clinics, of which 483 (median age 40 years; IQR 31-49) were included in the main analysis (226 collected with Evalyn Brush and 257 with Qvintip). Cervical samples were collected with Cervex-Brush. Colposcopy and histology outcomes were considered as the reference standard.Xpert HPV had similar accuracy for CIN2+ on self-collected versus clinician-collected samples (relative sensitivity=0.96 [95% CI 0.91-1.02], relative speci...
Source: Journal of Molecular Diagnostics - June 22, 2023 Category: Pathology Authors: Ardashel Latsuzbaia, Davy Vanden Broeck, Severien Van Keer, Steven Weyers, Gilbert Donders, Jean Doyen, Wiebren Tjalma, Philippe De Sutter, Alex Vorsters, Marc Arbyn Tags: Regular Article Source Type: research
Characterization of Reference Materials for CYP3A4 and CYP3A5: A GeT-RM Collaborative Project
Pharmacogenetic testing for CYP3A4 is increasingly provided by clinical and research laboratories; however, only a limited number of quality control and reference materials are currently available for many of the CYP3A4 variants included in clinical tests. To address this need, the Division of Laboratory Systems, Centers for Disease Control and Prevention (CDC) based Genetic Testing Reference Material Coordination Program (GeT-RM), in collaboration with members of the pharmacogenetic testing and research communities and the Coriell Institute for Medical Research, has characterized 30 DNA samples derived from Coriell cell l...
Source: Journal of Molecular Diagnostics - June 22, 2023 Category: Pathology Authors: Andrea Gaedigk, Erin C. Boone, Amy J. Turner, Ron H.N. van Schaik, Dilyara Chernova, Wendy Y. Wang, Ulrich Broeckel, Caitlin A. Granfield, Jennell C. Hodge, Reynold C. Ly, Ty C. Lynnes, Matthew W. Mitchell, Ann M. Moyer, Jason Oliva, Lisa V. Kalman Tags: Regular Article Source Type: research
Validation of a High-Sensitivity Assay for Detection of Chimeric Antigen Receptor T-Cell Vectors Using Low-Partition Digital PCR Technology
We describe the development and analytical validation of a digital PCR assay for ultr asensitive detection of CAR constructs after treatment, circumventing known technical limitations of low-partitioning platforms. Primers and probes, designed for detection of axicabtagene, brexucabtagene, and Memorial Sloan Kettering CAR constructs, were employed to validate testing on the Bio-Rad d igital PCR low-partitioning platform; results were compared with Raindrop, a high-partitioning system, as reference method. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 15, 2023 Category: Pathology Authors: Maria E. Arcila, Utsav Patel, Amir Momeni-Boroujeni, JinJuan Yao, Roger Chan, Joe Chan, Ivelise Rijo, Wayne Yu, Nelio Chaves, Hina Patel, Srushti Kakadiya, Sean Lachhander, Brigitte Senechal, Isabelle C. Riviere, Xiuyan Wang, Michel Sadelain, Khedoudja Na Tags: Technical advance Source Type: research
Validation of a High sensitivity assay for detection of CAR T cell vectors using low partition digital PCR technology
We describe the development and analytical validation of a digital-PCR (dPCR) assay for ultra-sensitive detection of CAR constructs post-treatment, circumventing known technical limitations of low partitioning platforms.Primers and probes, designed for detection of axicabtagene, brexucabtagene and MSK CAR constructs, were employed to validate testing on the Bio-Rad dPCR low-partitioning platform; results were compared to Raindrop, a high-partitioning system, as reference method. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 15, 2023 Category: Pathology Authors: Maria E. Arcila, Utsav Patel, Amir Momeni-Boroujeni, JinJuan Yao, Roger Chan, Joe Chan, Ivelise Rijo, Wayne Yu, Nelio Chaves, Hina Patel, Srushti Kakadiya, Sean Lachhander, Brigitte Senechal, Isabelle C. Riviere, Xiuyan Wang, Michel Sadelain, Khedoudja Na Tags: Technical Advance Source Type: research
Evaluation of Sensitive Urine DNA-based PENK Methylation Test for Detecting Bladder Cancer in Patients with Hematuria
This study introduces and validates a highly sensitive urine-based DNA methylation test. The test improves sensitivity in detecting PENK methylation in urine DNA using Linear Target Enrichment (LTE) followed by quantitative methylation-specific PCR (qMSP) (mePENK-LTE/qMSP). (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 14, 2023 Category: Pathology Authors: Tae Jeong Oh, Ji Yong Lee, Yangyei Seo, Min A. Woo, Jae Sung Lim, Yong Gil Na, Ki Hak Song, Bo-Ram Bang, Justin Junguek Lee, Ju Hyun Shin, Sungwhan An Tags: Regular Article Source Type: research
Partitioning for Easy Multiplexing
Clinical genome-wide next-generation sequencing (NGS) has brought new challenges to genetic laboratories. The identification of numerous patient-specific variants that may require to be screened for on multiple other samples poses an issue when striving for time and cost-effectiveness. Here, we propose d-multiSeq, a straightforward method utilizing the advantages of droplet PCR for multiplexing combined with amplicon-based NGS. By comparing d-multiSeq with a standard multiplex amplicon-based NGS, we showed that partitioning prevents the amplification competition seen when multiplexing and leads to a homogeneous representat...
Source: Journal of Molecular Diagnostics - June 9, 2023 Category: Pathology Authors: Alexia Kinoo, Aur élie Caye-Eude, Yoann Vial, Hélène Cavé, Chloé Arfeuille Tags: Regular article Source Type: research
Partitioning for easy multiplexing: a versatile droplet PCR application for clone monitoring in tumors
Clinical genome-wide next generation sequencing (NGS) has brought new challenges to genetic laboratories. The identification of numerous patient-specific variants which may require to be screened for on multiple other samples poses an issue when striving for time and cost effectiveness. Here we propose d-multiSeq, a straightforward method utilizing the advantages of droplet PCR (dPCR) for multiplexing combined with amplicon-based NGS. By comparing d-multiSeq with a standard multiplex amplicon-based NGS we showed that partitioning prevents the amplification competition seen when multiplexing and lead to a homogeneous repres...
Source: Journal of Molecular Diagnostics - June 9, 2023 Category: Pathology Authors: Alexia Kinoo, Aur élie Caye-Eude, Yoann Vial, Hélène Cavé, Chloé Arfeuille Tags: Regular Article Source Type: research
