Analysis of Driver Mutational Hot Spots in Blood-Derived Cell-Free DNA of Patients with Primary Central Nervous System Lymphoma Obtained before Intracerebral Biopsy
In newly diagnosed systemic diffuse large B cell lymphoma (DLBCL) next generation sequencing of plasma derived cell free DNA (cfDNA) detects somatic mutations as accurate as genotyping of the tumor biopsy. A distinct DLBCL entity confined to the central nervous system (CNS) is primary CNS lymphoma (PCNSL), which requires intracerebral biopsy and neuropathological analysis to establish the diagnosis. So far, a biomarker for diagnosis and follow-up of PCNSL that can be investigated in blood has not been identified. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 30, 2020 Category: Pathology Authors: Manuel Montesinos-Rongen, Anna Brunn, Armin Tuchscherer, Peter Borchmann, Elisabeth Schorb, Benjamin Kasenda, Janine Altm üller, Gerald Illerhaus, Maximilian I. Ruge, Mohammad Maarouf, Reinhard Büttner, Martin-Leo Hansmann, Michael Hallek, Marco Prinz, Tags: Regular Article Source Type: research

Genetic Characterization of Pediatric Sarcomas by Targeted RNA Sequencing
Somatic variants, primarily fusion genes and single nucleotide variants (SNVs) or indels, are prevalent among sarcomas. In many cases, accurate diagnosis of these tumors incorporates genetic findings that may also carry prognostic or therapeutic significance. Using the Anchored Multiplex PCR based FusionPlex system, we developed a custom RNA sequencing panel that simultaneously detects fusion genes, SNVs and indels in 112 genes found to be recurrently mutated in solid tumors. Using this assay, we conducted a retrospective analysis to identify somatic variants that may have assisted with classifying a cohort of 90 previousl...
Source: Journal of Molecular Diagnostics - July 30, 2020 Category: Pathology Authors: Matthew R. Avenarius, Cecelia R. Miller, Michael A. Arnold, Selene Koo, Ryan Roberts, Martin Hobby, Thomas Grossman, Yvonne Moyer, Richard K. Wilson, Elaine R. Mardis, Julie M. Gastier-Foster, Ruthann Pfau Source Type: research

Performance of the Roche cobas MTB assay for the molecular diagnosis of pulmonary tuberculosis in a high HIV burden setting
There is a need to increase access to and improve sensitivities of methods for diagnosing Mycobacterium tuberculosis infection and for detecting rifampicin and isoniazid resistance. The performance of the new cobas MTB assay for use on cobas 6800/8800 Systems (Roche) was assessed in this study and compared to two other commercial assays: Real-Time MTB (Abbott), and Xpert MTB/RIF (Cepheid).Molecular PCR-based assays were conducted on sputum specimens collected from individuals with presumptive and confirmed TB (n=294) from two clinical facilities in South Africa from December 2016 to October 2017. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 30, 2020 Category: Pathology Authors: Lesley Scott, Anura David, Lyndel Govender, Jan Furrer, Modiehi Rakgokong, Ziyaad Waja, Neil Martinson, Gabriel Eisenberg, Elizabeth Marlowe, Wendy Stevens Tags: Regular Article Source Type: research

Analysis of Driver Mutational Hot Spots in Blood-Derived Cell-Free DNA of Patients with Primary Central Nervous System Lymphoma Obtained before Intracerebral Biopsy
In newly diagnosed systemic diffuse large B cell lymphoma (DLBCL) next generation sequencing of plasma derived cell free DNA (cfDNA) detects somatic mutations as accurate as genotyping of the tumor biopsy. A distinct DLBCL entity confined to the central nervous system (CNS) is primary CNS lymphoma (PCNSL), which requires intracerebral biopsy and neuropathological analysis to establish the diagnosis. So far, a biomarker for diagnosis and follow-up of PCNSL that can be investigated in blood has not been identified. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 30, 2020 Category: Pathology Authors: Manuel Montesinos-Rongen, Anna Brunn, Armin Tuchscherer, Peter Borchmann, Elisabeth Schorb, Benjamin Kasenda, Janine Altm üller, Gerald Illerhaus, Maximilian I. Ruge, Mohammad Maarouf, Reinhard Büttner, Martin-Leo Hansmann, Michael Hallek, Marco Prinz, Tags: Regular Article Source Type: research

Genetic Characterization of Pediatric Sarcomas by Targeted RNA Sequencing
Somatic variants, primarily fusion genes and single nucleotide variants (SNVs) or indels, are prevalent among sarcomas. In many cases, accurate diagnosis of these tumors incorporates genetic findings that may also carry prognostic or therapeutic significance. Using the Anchored Multiplex PCR based FusionPlex system, we developed a custom RNA sequencing panel that simultaneously detects fusion genes, SNVs and indels in 112 genes found to be recurrently mutated in solid tumors. Using this assay, we conducted a retrospective analysis to identify somatic variants that may have assisted with classifying a cohort of 90 previousl...
Source: Journal of Molecular Diagnostics - July 30, 2020 Category: Pathology Authors: Matthew R. Avenarius, Cecelia R. Miller, Michael A. Arnold, Selene Koo, Ryan Roberts, Martin Hobby, Thomas Grossman, Yvonne Moyer, Richard K. Wilson, Elaine R. Mardis, Julie M. Gastier-Foster, Ruthann Pfau Source Type: research

Proposal of RT-PCR –Based Mass Population Screening for Severe Acute Respiratory Syndrome Coronavirus 2 (Coronavirus Disease 2019)
This study investigated a sample pooling approach for feasibility and accuracy in a wide-scale population screening for coronavirus disease 2019. A total of 940 nasopharyngeal swab samples (934 negative and 6 positive) previously tested for SARS-CoV-2 were deidentified and assigned random numbers for analysis, and 94 pools of 10 samples each were generated. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 28, 2020 Category: Pathology Authors: Nikhil S. Sahajpal, Ashis K. Mondal, Allan Njau, Sudha Ananth, Kimya Jones, Pankaj K. Ahluwalia, Meenakshi Ahluwalia, Yasmeen Jilani, Alka Chaubey, Madhuri Hegde, Vamsi Kota, Amyn Rojiani, Ravindra Kolhe Tags: Regular article Source Type: research

Amplicon-Based Next-Generation Sequencing for Detection of Fungi in Formalin-Fixed, Paraffin-Embedded Tissues: Correlation with Histopathology and Clinical Applications
Invasive fungal infections are increasing in prevalence due to an expanding population of immunocompromised individuals. To reduce morbidity and mortality, it is critical to accurately identify fungal pathogens to guide treatment. Current methodologies rely on histopathology, fungal culture, and serology, which are often insufficient for diagnosis. Here we describe the use of a lab-developed internal transcribed spacer (ITS) targeted amplicon-based Next Generation Sequencing (NGS) assay for the identification of fungal etiology in fungal stain positive FFPE tissues by using Illumina MiSeq. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 28, 2020 Category: Pathology Authors: Paige M.K. Larkin, Katy L. Lawson, Deisy A. Contreras, Catherine Q. Le, Marisol Trejo, Susan Realegeno, Evann E. Hilt, Sukantha Chandrasekaran, Omai B. Garner, Gregory A. Fishbein, Shangxin Yang Source Type: research

Proposal of Reverse Transcription-PCR –Based Mass Population Screening for SARS-CoV-2 (COVID-19)
Testing for SARS-CoV-2 has lagged behind in many countries due to lack of adequate test kits and bottlenecks in the analytical process. The aim of this study was to investigate the feasibility and accuracy of a sample pooling approach for wide-scale population screening for COVID-19. A total of 940 nasopharyngeal-swab samples (934 negative and 6 positive) previously tested for SARS-CoV-2 were de-identified and assigned random numbers for analysis. From this, 94 pools of 10 samples each were created. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 28, 2020 Category: Pathology Authors: Nikhil Shri Sahajpal, Ashis K. Mondal, Allan Njau, Sudha Ananth, Kimya Jones, Pankaj K. Ahluwalia, Meenakshi Ahluwalia, Yasmeen Jilani, Alka Chaubey, Madhuri Hegde, Vamsi Kota, Amyn Rojiani, Ravindra Kolhe Source Type: research

Amplicon-Based Next-Generation Sequencing for Detection of Fungi in Formalin-Fixed, Paraffin-Embedded Tissues: Correlation with Histopathology and Clinical Applications
Invasive fungal infections are increasing in prevalence due to an expanding population of immunocompromised individuals. To reduce morbidity and mortality, it is critical to accurately identify fungal pathogens to guide treatment. Current methodologies rely on histopathology, fungal culture, and serology, which are often insufficient for diagnosis. Here we describe the use of a lab-developed internal transcribed spacer (ITS) targeted amplicon-based Next Generation Sequencing (NGS) assay for the identification of fungal etiology in fungal stain positive FFPE tissues by using Illumina MiSeq. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 28, 2020 Category: Pathology Authors: Paige M.K. Larkin, Katy L. Lawson, Deisy A. Contreras, Catherine Q. Le, Marisol Trejo, Susan Realegeno, Evann E. Hilt, Sukantha Chandrasekaran, Omai B. Garner, Gregory A. Fishbein, Shangxin Yang Source Type: research

Proposal of Reverse Transcription-PCR –Based Mass Population Screening for SARS-CoV-2 (COVID-19)
Testing for SARS-CoV-2 has lagged behind in many countries due to lack of adequate test kits and bottlenecks in the analytical process. The aim of this study was to investigate the feasibility and accuracy of a sample pooling approach for wide-scale population screening for COVID-19. A total of 940 nasopharyngeal-swab samples (934 negative and 6 positive) previously tested for SARS-CoV-2 were de-identified and assigned random numbers for analysis. From this, 94 pools of 10 samples each were created. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 28, 2020 Category: Pathology Authors: Nikhil Shri Sahajpal, Ashis K. Mondal, Allan Njau, Sudha Ananth, Kimya Jones, Pankaj K. Ahluwalia, Meenakshi Ahluwalia, Yasmeen Jilani, Alka Chaubey, Madhuri Hegde, Vamsi Kota, Amyn Rojiani, Ravindra Kolhe Source Type: research

Editorial Board
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 23, 2020 Category: Pathology Source Type: research

Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 23, 2020 Category: Pathology Source Type: research

Clinical Evaluation of BD MAX MDR-TB Assay for Direct Detection of Mycobacterium tuberculosis Complex and Resistance Markers
This study assessed the assay ’s diagnostic accuracy by using pre-characterized MTBC culture–negative (n = 257), smear-negative/MTBC culture–positive (n = 93), and smear-positive/MTBC culture–positive (n = 153) respiratory specimens. Compared with culture, the overall sensitivity and specificity of BD MAX MDR-TB were 86.6% and 100%, respectively; sensitivities for smear-positive and smear-negative samples were 100% and 64.5%. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 16, 2020 Category: Pathology Authors: Sabine Hofmann-Thiel, Sara Plesnik, Marina Mihalic, Marion Hei ß-Neumann, Korkut Avsar, Markus Beutler, Harald Hoffmann Tags: Regular article Source Type: research

ACKR1 Alleles at 5.6 kb in a Well-Characterized Renewable US Food and Drug Administration (FDA) Reference Panel for Standardization of Blood Group Genotyping
The glycoprotein encoded by the ACKR1 gene expresses the Duffy blood group antigens and is a receptor for malaria parasites. We recently described 18 long-range ACKR1 alleles in an autochthonous population of a malaria endemic region. Extending this work, we sequenced the gene in a 53-sample repository established by the US Food and Drug Administration (FDA) as reference reagents for blood group genotyping. The FDA samples have been characterized for 19 genes; however, long-range haplotype information for these genes, including ACKR1, was lacking. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 16, 2020 Category: Pathology Authors: Kshitij Srivastava, Pavel P. Khil, Emilia Sippert, Evgeniya Volkova, John P. Dekker, Maria Rios, Willy A. Flegel Tags: Regular article Source Type: research

Early prediction of subsequent molecular response to nilotinib in patients with chronic myeloid leukemia: Comparison of the quantification of BCR-ABL1 ratios using ABL1 or GUSB control genes
The molecular monitoring of BCR-ABL1 transcripts is a critical prognostic indicator of treatment response in chronic myeloid leukemia (CML). The quantification of BCR-ABL1 transcripts using ABL1 or GUSB as control genes on the early molecular response (MR) to front-line nilotinib was studied using data from 60 patients with chronic phase CML from the ENEST1st substudy. The impact of BCR-ABL1/ABL1 and BCR-ABL1/GUSB ratios at early timepoints as independent variables on subsequent MR was determined by logistic regression analyses and predictive cut-off values determined by receiver operating curve analyses (ROC). (Source: Jo...
Source: Journal of Molecular Diagnostics - July 16, 2020 Category: Pathology Authors: Ruth Stuckey, Luis-Felipe Casado, Dolors Colomer, Mar ía Teresa Gómez-Casares, Laura Casas, Valentín García-Gutierrez, José Luis Sastre, Ángel Ramírez-Payer, Ferrán Vall-Llovera, María Ángeles Goñi, Blanca Xicoy, Ana Cristina Godoy, Javier Nú Tags: Regular Article Source Type: research

Clinical evaluation of BD MAX MDR TB assay for direct detection of Mycobacterium tuberculosis complex and resistance markers
In this study, we assessed its diagnostic accuracy using pre-characterized MTBC-culture negative (n=257), smear-negative / MTBC-culture positive (n=93), and smear-positive / MTBC-culture positive (n=153) respiratory specimens. Compared to culture, overall sensitivity and specificity of BD MAX MDR-TB were 86.6% and 100%, respectively; sensitivities for smear-positive and smear-negative samples were 100% and 64.5%, respectively. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 16, 2020 Category: Pathology Authors: Sabine Hofmann-Thiel, Sara Plesnik, Marina Mihalic, Marion Hei ß-Neumann, Korkut Avsar, Markus Beutler, Harald Hoffmann Source Type: research

ACKR1 alleles at 5.6 kb in a well-characterized renewable FDA reference panel for standardization of blood group genotyping
The glycoprotein encoded by the ACKR1 gene expresses the Duffy blood group antigens and is a receptor for malaria parasites. We recently described 18 long-range ACKR1 alleles in an autochthonous population of a malaria endemic region. Extending this work, we sequenced the gene in a 53 sample repository established by the FDA as reference reagents for blood group genotyping. The FDA samples have been characterized for 19 genes; however, long-range haplotype information for these genes, including ACKR1, was lacking. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 16, 2020 Category: Pathology Authors: Kshitij Srivastava, Pavel P. Khil, Emilia Sippert, Evgeniya Volkova, John P. Dekker, Maria Rios, Willy A. Flegel Source Type: research

Early prediction of subsequent molecular response to nilotinib in patients with chronic myeloid leukemia: Comparison of the quantification of BCR-ABL1 ratios using ABL1 or GUSB control genes
The molecular monitoring of BCR-ABL1 transcripts is a critical prognostic indicator of treatment response in chronic myeloid leukemia (CML). The quantification of BCR-ABL1 transcripts using ABL1 or GUSB as control genes on the early molecular response (MR) to front-line nilotinib was studied using data from 60 patients with chronic phase CML from the ENEST1st substudy. The impact of BCR-ABL1/ABL1 and BCR-ABL1/GUSB ratios at early timepoints as independent variables on subsequent MR was determined by logistic regression analyses and predictive cut-off values determined by receiver operating curve analyses (ROC). (Source: Jo...
Source: Journal of Molecular Diagnostics - July 16, 2020 Category: Pathology Authors: Ruth Stuckey, Luis-Felipe Casado, Dolors Colomer, Mar ía Teresa Gómez-Casares, Laura Casas, Valentín García-Gutierrez, José Luis Sastre, Ángel Ramírez-Payer, Ferrán Vall-Llovera, María Ángeles Goñi, Blanca Xicoy, Ana Cristina Godoy, Javier Nú Tags: Regular Article Source Type: research

Who to Test, When, and for What
This article also showcases a patient case, outlining problems with the diagnostic process as it currently stands, and poses potential strategies on how this process may be improved. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 1, 2020 Category: Pathology Authors: Sejal Morjaria, Kimberle C. Chapin Tags: Perspectives Source Type: research

Who To Test, When, And For What: Why Diagnostic Stewardship in Infectious Diseases Matters
New rapid molecular diagnostic technologies for infectious diseases provide faster diagnostic test results and if used correctly, will enable more rapid delivery of care to patients. This perspective piece outlines how we can more effectively utilize this new technology-with a focus on collaborative team approaches and tools clinicians and laboratorians can use to optimally affect patient care. Here, we also showcase a patient case outlining problems with the diagnostic process as it currently stands and pose potential strategies on how we can try to improve this process. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 1, 2020 Category: Pathology Authors: Sejal Morjaria, Kimberle C. Chapin Tags: Perspectives Source Type: research

Improved Diagnosis of Rare Disease Patients through Systematic Detection of Runs of Homozygosity
Autozygosity is associated with an increased risk of genetic rare disease, thus being a relevant factor for clinical genetic studies. More than 2400 exome sequencing data sets were analyzed and screened for autozygosity on the basis of detection of>1 Mbp runs of homozygosity (ROHs). A model was built to predict if an individual is likely to be a consanguineous offspring (accuracy, 98%), and probability of consanguinity ranges were established according to the total ROH size. Application of the model resulted in the reclassification of the consanguinity status of 12% of the patients. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 29, 2020 Category: Pathology Authors: Leslie Matalonga, Steven Laurie, Anastasios Papakonstantinou, Davide Piscia, Elisabetta Mereu, Gemma Bullich, Rachel Thompson, Rita Horvath, Luis P érez-Jurado, Olaf Riess, Ivo Gut, Gert-Jan van Ommen, Hanns Lochmüller, Sergi Beltran, Rare Disease–Con Tags: Regular article Source Type: research

Improved diagnosis of rare disease patients through systematic detection of runs of homozygosity
Autozygosity is associated with an increased risk of genetic rare disease (RD), thus being a relevant factor for clinical genetic studies. More than 2400 ES datasets were analysed and screened for autozygosity based on detection of>1Mbp runs of homozygosity (ROH). A model was built to predict if an individual is likely to be a consanguineous offspring (accuracy 98%) and “probability of consanguinity” ranges were established according to the total ROH size. Application of the model resulted in the re-classification of the consanguinity status of 12% of the patients. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 29, 2020 Category: Pathology Authors: Leslie Matalonga, Steven Laurie, Anastasios Papakonstantinou, Davide Piscia, Elisabetta Mereu, Gemma Bullich, Rachel Thompson, Rita Horvath, Luis P érez-Jurado, Olaf Riess, Ivo Gut, Gert-Jan van Ommen, Hanns Lochmüller, Sergi Beltran, RD-Connect GPAP an Source Type: research

Prognostic and Predictive Molecular Biomarkers in Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) is a malignancy of B cells with a variable clinical course. Prognostication is important to place patients into different risk categories for guiding decisions on clinical management, to treat or not to treat. Although several clinical, cytogenetic, and molecular parameters have been established, in the past decade, a tremendous understanding of molecular lesions has been obtained with the advent of high-throughput sequencing. Meanwhile, rapid advances in the understanding of the CLL oncogenic pathways have led to the development of small-molecule targeting signal transducers, tyrosine-pr...
Source: Journal of Molecular Diagnostics - June 28, 2020 Category: Pathology Authors: Jimmy Lee, Y. Lynn Wang Tags: Review Source Type: research

A Role for Chromosomal Microarray Testing in the Workup of Male Infertility
Genetic analysis is a critical component in the male infertility workup. For male infertility due to oligospermia/azoospermia, standard guidelines recommend karyotype and Y-chromosome microdeletion analyses. A karyotype is used to identify structural and numerical chromosome abnormalities, whereas Y-chromosome microdeletions are commonly evaluated by multiplex PCR analysis because of their submicroscopic size. Because these assays often require different vacutainer tubes to be sent to different laboratories, ordering is prone to errors. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 28, 2020 Category: Pathology Authors: Kelsey J. McIntyre, Elissa Murphy, Lauren Mertens, Adrian M. Dubuc, Ruth A. Heim, Heather Mason-Suares Tags: Regular article Source Type: research

Specific gyrA Gene Mutations Correlate with High Prevalence of Discordant Levofloxacin Resistance in Mycobacterium tuberculosis Isolates from Beijing, China
This article determined the discordance rate of levofloxacin (LFX) resistance results, obtained via MeltPro TB molecular testing, versus pDST of clinical TB isolates collected in Beijing, China, between January and December 2018. Isolates with discordant results were further subjected to LFX minimal inhibitory concentration (MIC) determinations and DNA sequence analysis to explore causes of discordance. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 28, 2020 Category: Pathology Authors: Fengmin Huo, Yifeng Ma, Shanshan Li, Yi Xue, Yuanyuan Shang, Lingling Dong, Yunxu Li, Yu Pang Tags: Regular article Source Type: research

Specific gyrA gene mutations correlate with high prevalence of discordant levofloxacin resistance in Mycobacterium tuberculosis isolates from Beijing, China
Although rapid, highly sensitive molecular diagnostics tests are useful for diagnosing fluoroquinolone (FQ)-resistant tuberculosis (TB), results of molecular testing versus conventional sequential phenotypic drug susceptibility testing (pDST) are frequently discordant. Here we determined the discordance rate of levofloxacin (LFX) resistance results obtained via MeltPro TB molecular testing versus pDST of clinical TB isolates collected in Beijing, China between January and December 2018. Isolates with discordant results were further subjected to LFX minimal inhibitory concentration (MIC) determinations and DNA sequence anal...
Source: Journal of Molecular Diagnostics - June 28, 2020 Category: Pathology Authors: Fengmin Huo, Yifeng Ma, Shanshan Li, Yi Xue, Yuanyuan Shang, Lingling Dong, Yunxu Li, Yu Pang Tags: Regular Article Source Type: research

Prognostic and Predictive Molecular Biomarkers in Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) is a malignancy of B cells with a variable clinical course. Prognostication is important to place patients into different risk categories for guiding decisions on clinical management, to treat or not to treat. Although a number of clinical, cytogenetic and molecular parameters have been established, in the past decade, a tremendous understanding of molecular lesions has been obtained with the advent of high-throughput sequencing. Meanwhile, rapid advances in the understanding of the CLL oncogenic pathways have led to the development of small molecules targeting signal transducers, BTK and...
Source: Journal of Molecular Diagnostics - June 28, 2020 Category: Pathology Authors: Jimmy Lee, Y. Lynn Wang Tags: Review Source Type: research

A Role for Chromosomal Microarray Testing in the Workup of Male Infertility
Genetic analysis is a critical component in the male infertility workup. For male infertility due to oligo/azoospermia, standard guidelines recommend karyotype and Y-chromosome microdeletion analyses. A karyotype is used to identify structural and numerical chromosome abnormalities, while Y-chromosome microdeletions are commonly evaluated by multiplex PCR analysis due to their submicroscopic size. Since these assays often require different vacutainer tubes to be sent to different laboratories, ordering is prone to errors. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 28, 2020 Category: Pathology Authors: Kelsey J. McIntyre, Elissa Murphy, Lauren Mertens, Adrian M. Dubuc, Ruth A. Heim, Heather Mason-Suares Source Type: research

Targeted Informatics for Optimal Detection, Characterization, and Quantification of FLT3 Internal Tandem Duplications Across Multiple Next-Generation Sequencing Platforms
In this study, data from multiple NGS platforms —anchored multiplex PCR (AMP), amplicon [TruSeq Custom Amplicon (TSCA)], and hybrid-capture—were analyzed through a custom algorithm, including platform-specific measures of AR. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 26, 2020 Category: Pathology Authors: Harrison K. Tsai, Diane G. Brackett, David Szeto, Ryan Frazier, Allison MacLeay, Phani Davineni, Danielle K. Manning, Elizabeth Garcia, Neal I. Lindeman, Long P. Le, Jochen K. Lennerz, Christopher J. Gibson, R. Coleman Lindsley, Annette S. Kim, Valentina Tags: Regular article Source Type: research

Development and Clinical Validation of a 90-Gene Expression Assay for Identifying Tumor Tissue Origin
The accurate identification of tissue origin in patients with metastatic cancer is critical for effective treatment selection but remains a challenge. The aim of this study is to develop a gene expression assay for tumor molecular classification and integrate it with clinicopathologic evaluations to identify the tissue origin for cancer of uncertain primary (CUP). A 90-gene expression signature, covering 21 tumor types, was identified and validated with an overall accuracy of 89.8% (95% CI, 0.87 –0.92) in 609 tumor samples. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 26, 2020 Category: Pathology Authors: Qing Ye, Qifeng Wang, Peng Qi, Jinying Chen, Yifeng Sun, Shichai Jin, Wanli Ren, Chengshu Chen, Mei Liu, Midie Xu, Gang Ji, Jun Yang, Ling Nie, Qinghua Xu, Deshuang Huang, Xiang Du, Xiaoyan Zhou Tags: Regular article Source Type: research

Targeted Informatics for Optimal Internal Tandem Duplications in FLT3 Detection, Characterization, and Quantification Across Multiple Next-Generation Sequencing Platforms
In this study, data from multiple NGS platforms —anchored multiplex PCR (AMP), amplicon (TSCA), and hybrid-capture—were analyzed through a custom algorithm, including platform-specific measures of AR. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 26, 2020 Category: Pathology Authors: Harrison K. Tsai, Diane Brackett, David Szeto, Ryan Frazier, Allison MacLeay, Phani Davineni, Danielle Manning, Elizabeth Garcia, Neal I. Lindeman, Long P. Le, Jochen K. Lennerz, Chris J. Gibson, R. Coleman Lindsley, Annette S. Kim, Valentina Nardi Tags: Regular article Source Type: research

High-Throughput Molecular Cancer Cell Line Characterization Using Digital Multiplex Ligation-Dependent Probe Amplification for Improved Standardization of in  Vitro Research
Tumor cell lines are widely used for cancer research, but challenges regarding quality control of cell line identity, cross contamination, and tumor somatic molecular stability remain, demanding novel approaches beyond conventional short tandem repeat profiling. A total of 21 commonly used multiple myeloma cell lines obtained from public repositories were analyzed by digital multiplex ligation-dependent probe amplification (digitalMLPA) to characterize germline single-nucleotide polymorphisms, insertions/deletions, and somatic copy number aberrations (CNAs). (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 26, 2020 Category: Pathology Authors: Karen Menezes, Lilit Atanesyan, Amy L. Sherborne, Maryvonne Steenkamer, Ivo Clemens, Suvi Savola, Martin F. Kaiser Tags: Regular article Source Type: research

Targeted Informatics for Optimal Internal Tandem Duplications in FLT3 Detection, Characterization, and Quantification Across Multiple Next-Generation Sequencing Platforms
In this study, data from multiple NGS platforms —anchored multiplex PCR (AMP), amplicon (TSCA), and hybrid-capture—were analyzed through a custom algorithm, including platform-specific measures of AR. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 26, 2020 Category: Pathology Authors: Harrison K. Tsai, Diane Brackett, David Szeto, Ryan Frazier, Allison MacLeay, Phani Davineni, Danielle Manning, Elizabeth Garcia, Neal I. Lindeman, Long P. Le, Jochen K. Lennerz, Chris J. Gibson, R. Coleman Lindsley, Annette S. Kim, Valentina Nardi Tags: Regular article Source Type: research

Development and Clinical Validation of a 90-Gene Expression Assay for Identifying Tumor Tissue Origin
In this study, we aim to develop a gene expression assay for tumor molecular classification and integrate it with clinicopathological evaluations to identify the tissue origin for cancer of uncertain primary (CUP). A 90-gene expression signature covering 21 tumor types was identified and validated with an overall accuracy of 89.8% (95% CI, 0.87-0.92) in 609 tumor samples. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 26, 2020 Category: Pathology Authors: Qing Ye, Qifeng Wang, Peng Qi, Jinying Chen, Yifeng Sun, Shichai Jin, Wanli Ren, Chengshu Chen, Mei Liu, Midie Xu, Gang Ji, Jun Yang, Ling Nie, Qinghua Xu, Deshuang Huang, Xiang Du, Xiaoyan Zhou Tags: Regular Article Source Type: research

Targeted informatics for optimal FLT3-ITD detection, characterization, and quantification across multiple NGS platforms.
In this study, data from multiple NGS platforms -- anchored multiplex PCR (AMP), amplicon (TSCA), and hybrid-capture (HC) – was analyzed through a custom algorithm including platform-specific measures of allelic ratio. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 26, 2020 Category: Pathology Authors: Harrison K. Tsai, Diane Brackett, David Szeto, Ryan Frazier, Allison MacLeay, Phani Davineni, Danielle Manning, Elizabeth Garcia, Neal I. Lindeman, Long P. Le, Jochen K. Lennerz, Chris J. Gibson, R. Coleman Lindsley, Annette S. Kim, Valentina Nardi Tags: Regular Article Source Type: research

High-throughput molecular cancer cell line characterization using digital multiplex ligation-dependent probe amplification for improved standardization of in vitro research
Tumour cell lines are widely used for cancer research, but challenges regarding quality control of cell line identity, cross-contamination and tumour somatic molecular stability remain, demanding novel approaches beyond conventional short tandem repeat profiling. We analyzed 21 commonly used multiple myeloma (MM) cell lines obtained from public repositories by digital multiplex ligation-dependent probe amplification (digitalMLPA) to characterise germline single nucleotide (SNP), insertion/deletion polymorphisms (indels) and somatic copy number aberrations (CNA). (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 26, 2020 Category: Pathology Authors: Karen Menezes, Lilit Atanesyan, Amy L. Sherborne, Maryvonne Steenkamer, Ivo Clemens, Suvi Savola, Martin F. Kaiser Tags: Regular Article Source Type: research

Editorial Board
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 22, 2020 Category: Pathology Source Type: research

Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 22, 2020 Category: Pathology Source Type: research

Poly (ADP Ribose) Polymerase Inhibitors for Cancer
Defects in homologous recombination (HR) pathway members play a major role in tumorigenesis and predisposition to cancer. HR deficiency (HRD) confers cellular susceptibility to agents that promote cytotoxic double-strand breaks (DSBs); this principle has led to the development and approval of poly (ADP ribose) polymerase (PARP) inhibitors for use in BRCA-mutant breast and ovarian cancers. PARP inhibitors are currently subject to>100 ongoing clinical trials in a wide spectrum of cancer types. Although these approvals have injected new excitement into the field, many challenges remain in detection and interpretation of cl...
Source: Journal of Molecular Diagnostics - June 19, 2020 Category: Pathology Authors: Lynette M. Sholl, Diana Mandelker, Tracy Stockley Tags: Practice Advances Source Type: research

PARP inhibitors for Cancer: Essential Biologic, Diagnostic, and Therapeutic Concepts for Today ’s Practitioner
The PARPi Series Content Committee is a working group of the Association for Molecular Pathology (AMP) Training and Education Committee. The PARPi Series Content Committee members consisted of Diana Mandelker, Lynette Sholl (Chair) and Tracy Stockley. The 2020 Training and Education Committee consisted of Yassmine Akkari (Chair), Barbara Anderson, Nathanael Bailey (Chair-elect), Gerald Capraro, Alanna Church, Annie Garcia, Erin Graf, Lisa Haley, Sabah Kadri, Kristin Hunt Karner, Christian Kunder, Nathan Montgomery, Honey Reddi, Lauren Ritterhouse, Cinthya Zepeda-Mendoza, and Weiwei Zhang. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 19, 2020 Category: Pathology Authors: Lynette Sholl, Diana Mandelker, Tracy Stockley Tags: Other Source Type: research

Responding to the Challenges of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Clinical molecular laboratory professionals are at the frontline of the response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, providing accurate, high-quality laboratory results to aid in diagnosis, treatment, and epidemiology. In this role, we have encountered numerous regulatory, reimbursement, supply-chain, logistical, and systems challenges that we have struggled to overcome to fulfill our calling to provide patient care. In this Perspective from the Association for Molecular Pathology Infectious Disease Subdivision Leadership team, we review how our members have  risen to these ch...
Source: Journal of Molecular Diagnostics - June 17, 2020 Category: Pathology Authors: Frederick S. Nolte, N. Esther Babady, Blake W. Buchan, Gerald A. Capraro, Erin H. Graf, Amy L. Leber, Erin McElvania, Joseph D.C. Yao Tags: Perspectives Source Type: research

Responding to the Challenges of SARS-CoV-2: Perspectives from the Association for Molecular Pathology (AMP) Infectious Disease Subdivision Leadership
Clinical molecular laboratory professionals are at the frontline of the response to the SARS-CoV-2 pandemic, providing accurate, high-quality laboratory results to aid in diagnosis, treatment, and epidemiology. In this role, we have encountered numerous regulatory, reimbursement, supply-chain, logistical, and systems challenges that we have struggled to overcome in order to fulfill our calling to provide patient care. In this Perspective from the Association for Molecular Pathology Infectious Disease Subdivision Leadership team we review how our members have risen to these challenges, provide recommendations for managing t...
Source: Journal of Molecular Diagnostics - June 17, 2020 Category: Pathology Authors: Frederick S. Nolte, N. Esther Babady, Blake W. Buchan, Gerald A. Capraro, Erin H. Graf, Amy L. Leber, Erin McElvania, Joseph D.C. Yao Tags: Perspectives Source Type: research

Comparative Evaluation of Five Assays for Detection of Carbapenemases with a Proposed Scheme for Their Precise Application
The escalating problem of the dissemination of carbapenemase-producing bacteria (CPB) has gained worldwide attention. The prompt diagnosis of CPB and precise identification of carbapenemases are imperative to enable specific antibiotic therapy and control the spread of these bacteria. The present study was designed to assess the performance of five important assays for the detection of carbapenemases. The modified carbapenem inactivation method (mCIM), CARBA-5, GeneXpert Carba-R, BD  MAX Check-Points CPO, and GeneFields CPE assays were evaluated with an international collection of 159 bacterial isolates, inc...
Source: Journal of Molecular Diagnostics - June 14, 2020 Category: Pathology Authors: Hazim O. Khalifa, Takashi Okanda, Amer Ali Abd El-Hafeez, Amera Abd El Latif, Ahmed G.K. Habib, Hisakazu Yano, Yasuyuki Kato, Tetsuya Matsumoto Tags: Regular article Source Type: research

Clinical Service Delivery of Noninvasive Prenatal Diagnosis by Relative Haplotype Dosage for Single-Gene Disorders
A relative haplotype dosage (RHDO) –based method was developed and implemented into routine clinical practice for noninvasive prenatal diagnosis (NIPD) of multiple single-gene disorders: spinal muscular atrophy, Duchenne and Becker muscular dystrophies, and cystic fibrosis. This review describes the experiences of the first 152 pre gnancies to have NIPD by RHDO as part of a routine clinical service. Provision of results within a clinically useful time frame (mean, 11 calendar days) was shown to be possible, and the failure rate was low (4%), none being due to a technical failure. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 14, 2020 Category: Pathology Authors: Elizabeth Young, Benjamin Bowns, Amy Gerrish, Michael Parks, Samantha Court, Samuel Clokie, Chipo Mashayamombe-Wolfgarten, Julie Hewitt, Denise Williams, Trevor Cole, Stephanie Allen Tags: Regular article Source Type: research

Comparative Evaluation of five Assays for Detection of Carbapenemases with a Proposed Scheme for Their Precise Application
The escalating problem of the dissemination of carbapenemase-producing bacteria (CPB) has gained worldwide attention. The prompt diagnosis of CPB and precise identification of carbapenemases are imperative to enable specific antibiotic therapy and control the spread of these bacteria. The present study was designed to assess the performance of five important assays for the detection of carbapenemases. The mCIM, CARBA-5, Xpert Carba-R, BD MAX Check-Points CPO, and GeneFields CPE assays were evaluated with an international collection of 159 bacterial isolates, including 93 CPB and 66 non-CPB isolates. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 14, 2020 Category: Pathology Authors: Hazim O. Khalifa, Takashi Okanda, Amer Ali Abd El-Hafeez, Amera Abd El Latif, Ahmed G.K. Habib, Hisakazu Yano, Yasuyuki Kato, Tetsuya Matsumoto Tags: Regular Article Source Type: research

Clinical service delivery of non-invasive prenatal diagnosis (NIPD) by relative haplotype dosage (RHDO) for single gene disorders
We have developed and implemented into routine clinical practice a relative haplotype dosage (RHDO) based method for non-invasive prenatal diagnosis (NIPD) of multiple single gene disorders: spinal muscular atrophy (SMA), Duchenne and Becker muscular dystrophies (DMD/BMD) and cystic fibrosis (CF). This review describes our experience of the first 152 pregnancies to have NIPD by RHDO as part of a routine clinical service. We have demonstrated that it is possible to provide a result within a clinically useful timeframe (mean 11 calendar days) with a very low failure rate (4%), none being due to a technical failure. (Source: ...
Source: Journal of Molecular Diagnostics - June 14, 2020 Category: Pathology Authors: Elizabeth Young, Benjamin Bowns, Amy Gerrish, Michael Parks, Samantha Court, Samuel Clokie, Chipo Mashayamombe-Wolfgarten, Julie Hewitt, Denise Williams, Trevor Cole, Stephanie Allen Tags: Regular Article Source Type: research