Editorial Board
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 20, 2017 Category: Pathology Source Type: research

Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 20, 2017 Category: Pathology Source Type: research

Highly Multiplex Real-Time PCR –Based Screening for Blood-Borne Pathogens on an OpenArray Platform
Molecular diagnostics are increasingly used in the blood bank industry. A device that can combine simultaneous detection of multiple targets with the flexibility of inclusion of emerging pathogens is desirable for testing blood products. A highly multiplexed blood-borne pathogen panel (BBPP) using dual-label probe chemistry (TaqMan assays) was developed for simultaneous detection and discrimination of 17 viral pathogens in human plasma samples and 13 bacterial and protozoan pathogens in human blood samples on the OpenArray platform. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - June 14, 2017 Category: Pathology Authors: Elena Grigorenko, Carolyn Fisher, Sunali Patel, Valerie Winkelman, Phillip Williamson, Caren Chancey, Germ án Añez, Maria Rios, Victoria Majam, Sanjai Kumar, Robert Duncan Tags: Regular Article Source Type: research

PheoSeq
This study aimed to optimize targeted NGS in PPGL genetic diagnostics. A workflow based on two customized targeted NGS assays was validated to study the 18 main PPGL genes in germline and frozen tumor DNA, with one of them specifically directed toward formalin-fixed, paraffin-embedded tissue. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - May 25, 2017 Category: Pathology Authors: Maria Curr ás-Freixes, Elena Piñeiro-Yañez, Cristina Montero-Conde, María Apellániz-Ruiz, Bruna Calsina, Veronika Mancikova, Laura Remacha, Susan Richter, Tonino Ercolino, Natalie Rogowski-Lehmann, Timo Deutschbein, María Calatayud, Sonsoles Guadali Tags: Regular Article Source Type: research

Validation of a Next-Generation Sequencing Pipeline for the Molecular Diagnosis of Multiple Inherited Cancer Predisposing Syndromes
Despite the growing knowledge of the genetic background behind the cancers that occur in a context of hereditary predisposition, personal or family cancer history may not be clear enough to support directional gene testing. Defined targeted next-generation sequencing gene panels allow identification of the causative disease mutations of multigene syndromes and differential diagnosis for syndromes with phenotypically overlapping characteristics. Herein, we established a next-generation sequencing analysis pipeline for the molecular diagnosis of multiple inherited cancer predisposing syndromes using the commercially availabl...
Source: Journal of Molecular Diagnostics - May 18, 2017 Category: Pathology Authors: Paula Paulo, Pedro Pinto, Ana Peixoto, Catarina Santos, Carla Pinto, Patr ícia Rocha, Isabel Veiga, Gabriela Soares, Catarina Machado, Fabiana Ramos, Manuel R. Teixeira Tags: Regular Article Source Type: research

Minimal Residual Disease Monitoring of Acute Myeloid Leukemia by Massively Multiplex Digital PCR in Patients with NPM1 Mutations
The presence of minimal residual disease (MRD) is widely recognized as a powerful predictor of therapeutic outcome in acute myeloid leukemia (AML), but methods of measurement and quantification of MRD in AML are not yet standardized in clinical practice. There is an urgent, unmet need for robust and sensitive assays that can be readily adopted as real-time tools for disease monitoring. NPM1 frameshift mutations are an established MRD marker present in half of patients with cytogenetically normal AML. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - May 16, 2017 Category: Pathology Authors: Nuria Mencia-Trinchant, Yang Hu, Maria Antonina Alas, Fatima Ali, Bas J. Wouters, Sangmin Lee, Ellen K. Ritchie, Pinkal Desai, Monica L. Guzman, Gail J. Roboz, Duane C. Hassane Tags: Regular Article Source Type: research

Simultaneous Genotyping of α-Thalassemia Deletional and Nondeletional Mutations by Real-Time PCR–Based Multicolor Melting Curve Analysis
We report a novel real-time PCR–based assay that can simultaneously genotype four major deletional and three common nondeletional mutations in two parallel reactions by using multicolo r melting curve analysis. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - May 12, 2017 Category: Pathology Authors: Qiuying Huang, Xudong Wang, Ning Tang, Tizhen Yan, Ping Chen, Qingge Li Tags: Regular Article Source Type: research

Study of Preanalytic and Analytic Variables for Clinical Next-Generation Sequencing of Circulating Cell-Free Nucleic Acid
Detection of mutations in plasma circulating cell-free DNA (cfDNA) by next-generation sequencing (NGS) has opened up new possibilities for monitoring treatment response and disease progression in patients with solid tumors. However, implementation of cfDNA genotyping in diagnostic laboratories requires systematic assessment of preanalytical parameters and analytical performance of NGS platforms. We assessed the effects of peripheral blood collection tube and plasma separation time on cfDNA yield and integrity and performance of the Ion PGM, Proton, and MiSeq NGS platforms. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - May 12, 2017 Category: Pathology Authors: Meenakshi Mehrotra, Rajesh R. Singh, Wei Chen, Richard S.P. Huang, Alaa A. Almohammedsalim, Bedia A. Barkoh, Crystal M. Simien, Marcos Hernandez, Carmen Behrens, Keyur P. Patel, Mark J. Routbort, Russell R. Broaddus, L. Jeffrey Medeiros, Ignacio I. Wistub Tags: Regular Article Source Type: research

Concordance between Research Sequencing and Clinical Pharmacogenetic Genotyping in the eMERGE-PGx Study
There has been extensive debate about both the necessity of orthogonal confirmation of next-generation sequencing (NGS) results in Clinical Laboratory Improvement Amendments –approved laboratories and return of research NGS results to participants enrolled in research studies. In eMERGE-PGx, subjects underwent research NGS using PGRNseq and orthogonal targeted genotyping in clinical laboratories, which prompted a comparison of genotyping results between platforms. Con cordance (percentage agreement) was reported for 4077 samples tested across nine combinations of research and clinical laboratories. (Source: Journal o...
Source: Journal of Molecular Diagnostics - May 11, 2017 Category: Pathology Authors: Laura J. Rasmussen-Torvik, Berta Almoguera, Kimberly F. Doheny, Robert R. Freimuth, Adam S. Gordon, Hakon Hakonarson, Jared B. Hawkins, Ammar Husami, Lynn Ivacic, Iftikhar J. Kullo, Michael D. Linderman, Teri A. Manolio, Aniwaa O. Obeng, Renata Pellegrino Tags: Regular Article Source Type: research

Utility of NIST Whole-Genome Reference Materials for the Technical Validation of a Multigene Next-Generation Sequencing Test
The sensitivity and specificity of next-generation sequencing laboratory developed tests (LDTs) are typically determined by an analyte-specific approach. Analyte-specific validations use disease-specific controls to assess an LDT's ability to detect known pathogenic variants. Alternatively, a methods-based approach can be used for LDT technical validations. Methods-focused validations do not use disease-specific controls but use benchmark reference DNA that contains known variants (benign, variants of unknown significance, and pathogenic) to assess variant calling accuracy of an NGS workflow. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - May 11, 2017 Category: Pathology Authors: Bennett O.V. Shum, Ilya Henner, Daniele Belluoccio, Marcus J. Hinchcliffe Tags: Regular Article Source Type: research

Improving Mutation Screening in Patients with Colorectal Cancer Predisposition Using Next-Generation Sequencing
Identification of genetic alterations is important for family risk assessment in colorectal cancers. Next-generation sequencing (NGS) technologies provide useful tools for single-nucleotide and copy number variation (CNV) identification in many genes and samples simultaneously. Herein, we present the validation of current Multiplicom MASTR designs of mismatch repair combined to familial adenomatous polyposis genes in a single PCR reamplification test for eight DNA samples simultaneously on a MiSeq apparatus. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - May 11, 2017 Category: Pathology Authors: Jean-Marc Rey, Vincent Ducros, Pascal Pujol, Qing Wang, Marie-Pierre Buisine, Hanaa Aissaoui, Thierry Maudelonde, Sylviane Olschwang Tags: Regular Article Source Type: research

Technical Validation of a Next-Generation Sequencing Assay for Detecting Clinically Relevant Levels of Breast Cancer –Related Single-Nucleotide Variants and Copy Number Variants Using Simulated Cell-Free DNA
Next-generation sequencing (NGS) is commonly used in a clinical setting for diagnostic and prognostic testing of genetic mutations to select optimal targeted therapies. Herein, we describe the development of a custom NGS assay for detecting single-nucleotide variants (SNVs) and copy number variations (CNVs) in a panel of 51 genes related to breast cancer. We designed and implemented a validation strategy in accordance with principles and guidelines developed by the Next-Generation Sequencing: Standardization of Clinical Testing work group using artificial, cell-free DNA (cfDNA) with mutant fragments prepared in a simple, r...
Source: Journal of Molecular Diagnostics - May 11, 2017 Category: Pathology Authors: Xin Yang, Yuxing Chu, Rui Zhang, Yanxi Han, Lucheng Zhang, Yu Fu, Dan Li, Rongxue Peng, Dongdong Li, Jiansheng Ding, Ziyang Li, Meiru Zhao, Kuo Zhang, Tian Lu, Lang Yi, Qisheng Wu, Guigao Lin, Jiehong Xie, Tao Liu, Ling Yang, Xin Yi, Jinming Li Tags: Regular Article Source Type: research

Molecular Diagnosis of Mosaic Overgrowth Syndromes Using a Custom-Designed Next-Generation Sequencing Panel
Recent studies have discovered a group of overgrowth syndromes, such as congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies (CLOVES) syndrome, Proteus syndrome, and megalencephaly-capillary malformation-polymicrogyria (MCAP) syndrome, are caused by somatic activating variants in the genes involved in the phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin pathway. Because of the low-abundance nature of these pathogenic variants, Sanger sequencing often yields negative results. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - May 11, 2017 Category: Pathology Authors: Fengqi Chang, Liu Liu, Erica Fang, Guangcheng Zhang, Tiansheng Chen, Kajia Cao, Yanchun Li, Marilyn M. Li Tags: Regular Article Source Type: research

Overgrowth Syndromes Caused by Somatic Variants in the Phosphatidylinositol 3-Kinase/AKT/Mammalian Target of Rapamycin Pathway
Somatic variants have been well described in tumorigenesis; however, they are only recently appreciated in other human disorders, such as mosaic overgrowth syndromes. Although overgrowth is a manifestation in many genetic syndromes, not all overgrowth syndromes are inherited. Mosaic somatic variants have been lately described in several overgrowth disorders, such as Proteus syndrome, CLOVES (congenital, lipomatous, overgrowth, vascular malformations, epidermal nevi, and spinal/skeletal anomalies and/or scoliosis) syndrome, megalencephaly –polymicrogyria-polydactyly-hydrocephalus syndrome, and megalencephaly–cap...
Source: Journal of Molecular Diagnostics - May 11, 2017 Category: Pathology Authors: Gozde Akgumus, Fengqi Chang, Marilyn M. Li Tags: Review Source Type: research

Development and Clinical Utility of a Blood-Based Test Service for the Rapid Identification of Actionable Mutations in Non –Small Cell Lung Carcinoma
This study validates a blood-based genome-testing service that provides accurate results within 72 hours. We focused on targetable variants in advanced non –small cell lung carcinoma—epidermal growth factor receptor gene (EGFR) variant L858R, exon 19 deletion (ΔE746−A750), and T790M; GTPase Kirsten ras gene (KRAS) variants G12C/D/V; and echinoderm microtubule associated protein like and 4 anaplastic lymphoma receptor tyrosine kinase fusion (EM L4-ALK) transcripts 1/2/3. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - April 19, 2017 Category: Pathology Authors: Hestia Mellert, Trudi Foreman, Leisa Jackson, Dianna Maar, Scott Thurston, Kristina Koch, Amanda Weaver, Samantha Cooper, Nicholas Dupuis, Ubaradka G. Sathyanarayana, Jakkie Greer, Westen Hahn, Dawne Shelton, Paula Stonemetz, Gary A. Pestano Tags: Regular article Source Type: research

Haplotype Counting for Sensitive Chimerism Testing
Fields of forensics, transplantation, and paternity rely on human identity testing. Currently, this is accomplished through amplification of microsatellites followed by capillary electrophoresis. An alternative and theoretically better approach uses multiple single-nucleotide polymorphisms located within a small region of DNA, a method we initially developed using HLA-A and called haplotype counting. Herein, we validated seven additional polymorphic loci, sequenced a total of 45 individuals from three of the 1000 Genomes populations (15 from each), and determined the number of haplotypes, heterozygosity, and polymorphic in...
Source: Journal of Molecular Diagnostics - April 19, 2017 Category: Pathology Authors: Marija Debeljak, Evelina Mocci, Max C. Morrison, Aparna Pallavajjalla, Katie Beierl, Marie Amiel, Micha ël Noë, Laura D. Wood, Ming-Tseh Lin, Christopher D. Gocke, Alison P. Klein, Ephraim J. Fuchs, Richard J. Jones, James R. Eshleman Tags: Regular article Source Type: research

Identification of NTRK3 Fusions in Childhood Melanocytic Neoplasms
We report herein the discovery of recurrent NTRK3 gene rearrangements in childhood melanocytic neoplasms with spitzoid and/or atypical features, based on genome-wide copy number analysis by single-nucleotide polymorphism array, which showed intragenic copy number changes in NTRK3. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - April 19, 2017 Category: Pathology Authors: Lu Wang, Klaus J. Busam, Ryma Benayed, Robert Cimera, Jiajing Wang, Ryan Denley, Mamta Rao, Ruth Aryeequaye, Kerry Mullaney, Long Cao, Marc Ladanyi, Meera Hameed Tags: Regular article Source Type: research

Utilization of Whole-Exome Next-Generation Sequencing Variant Read Frequency for Detection of Lesion-Specific, Somatic Loss of Heterozygosity in a Neurofibromatosis Type 1 Cohort with Tibial Pseudarthrosis
A subset of neurofibromatosis type 1 patients develop tibial dysplasia, which can lead to pseudarthrosis. The tissue from the tibial pseudarthrosis region commonly has a somatic second hit in NF1: single-nucleotide variants, small deletions, or loss of heterozygosity (LOH). We used exome next-generation sequencing (NGS) variant frequency data (allelic imbalance analysis) to detect somatic LOH in pseudarthrosis tissue from three individuals with clinically and diagnostically confirmed neurofibromatosis type 1, and verified the results with microarray. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - April 19, 2017 Category: Pathology Authors: Rebecca L. Margraf, Chad VanSant-Webb, David Sant, John Carey, Heather Hanson, Jacques D'Astous, Dave Viskochil, David A. Stevenson, Rong Mao Tags: Regular article Source Type: research

Correction
In the article entitled, “Microfluidic Platform for Single Nucleotide Polymorphism Genotyping of the Thiopurine S-Methyltransferase Gene to Evaluate Risk for Adverse Drug Events” (Volume 9, pages 521–529 of the September 2007 issue of The Journal of Molecular Diagnostics; http://dx.doi.org/10.2353/jmoldx.2007.070014), the second author's named was misspelled. The correct name is Govind V. Kaigala. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - April 19, 2017 Category: Pathology Tags: Correction Source Type: research

Correction
In the article entitled, “Amplicon Indel Hunter Is a Novel Bioinformatics Tool to Detect Large Somatic Insertion/Deletion Mutations in Amplicon-Based Next-Generation Sequencing Data” (Volume 17, 635–643 of the November 2015 issue of The Journal of Molecular Diagnostics; http://dx.doi.org/10.1016/j.jmoldx.2015.06.005) there is an update to the location of the AIH/AID toolkit. The software can now be found at https://github.com/skadri01/aiHunter. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - April 19, 2017 Category: Pathology Tags: Correction Source Type: research

Editorial Board
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - April 19, 2017 Category: Pathology Source Type: research

Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - April 19, 2017 Category: Pathology Source Type: research

Targeted Next-Generation Sequencing of 51 Genes Involved in Primary Electrical Disease
Primary electrical disease (PED) is characterized by cardiac arrhythmias, which can lead to sudden cardiac death in the absence of detectable structural heart disease. PED encompasses a diversity of inherited syndromes, predominantly Brugada syndrome, early repolarization syndrome, long QT syndrome, short QT syndrome, arrhythmogenic right ventricular cardiomyopathy, and catecholaminergic polymorphic ventricular tachycardia. To overcome the diagnostic challenges imposed by the clinical and genetic heterogeneity of PED, we developed a targeted gene panel for next-generation sequencing of 51 PED genes. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - March 21, 2017 Category: Pathology Authors: Dorien Proost, Johan Saenen, Geert Vandeweyer, Annelies Rotthier, Maaike Alaerts, Emeline M. Van Craenenbroeck, Joachim Van Crombruggen, Geert Mortier, Wim Wuyts, Christiaan Vrints, Jurgen Del Favero, Bart Loeys, Lut Van Laer Tags: Regular Article Source Type: research

Impact of Rapid Molecular Respiratory Virus Testing on Real-Time Decision Making in a Pediatric Emergency Department
Acute respiratory illnesses (ARIs) are usually viral [influenza, respiratory syncytial virus (RSV)] and account for 25% of emergency department (ED) peak-season visits. Laboratory respiratory PCR testing is accurate albeit slow for ED management, whereas rapid antigen testing is inaccurate. We determined the impact of bedside influenza/RSV PCR (molecular point-of-care test; mPOCT) on pediatric ARI management. This was a prospective cohort study of consecutive pediatric patients with ED-ordered respiratory PCR test, enrolled over 9 weeks during peak flu season. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - March 21, 2017 Category: Pathology Authors: Daniel T. Rogan, Mohit S. Kochar, Samuel Yang, James V. Quinn Tags: Regular Article Source Type: research

Guidelines for Validation of Next-Generation Sequencing –Based Oncology Panels
Next-generation sequencing (NGS) methods for cancer testing have been rapidly adopted by clinical laboratories. To establish analytical validation best practice guidelines for NGS gene panel testing of somatic variants, a working group was convened by the Association of Molecular Pathology with liaison representation from the College of American Pathologists. These joint consensus recommendations address NGS test development, optimization, and validation, including recommendations on panel content selection and rationale for optimization and familiarization phase conducted before test validation; utilization of reference c...
Source: Journal of Molecular Diagnostics - March 21, 2017 Category: Pathology Authors: Lawrence J. Jennings, Maria E. Arcila, Christopher Corless, Suzanne Kamel-Reid, Ira M. Lubin, John Pfeifer, Robyn L. Temple-Smolkin, Karl V. Voelkerding, Marina N. Nikiforova Tags: Special Article Source Type: research

Current and Emerging Molecular Tests for Human Papillomavirus –Related Neoplasia in the Genomic Era
Laboratory tests have a key role in preventing human papillomavirus (HPV) –driven carcinomas and in guiding therapeutic interventions. An understanding of the virology, immunology, and carcinogenesis of HPV is essential for choosing appropriate diagnostic test modalities and developing new and even more effective cancer prevention strategies. HPV infects basal epithelia l cells on multiple surfaces and induces carcinoma primarily in the cervix and the oropharynx. HPV types are stratified as high risk or low risk based on their carcinogenic potential, driven largely by viral interference with cell cycle regulation and...
Source: Journal of Molecular Diagnostics - March 19, 2017 Category: Pathology Authors: Sixto M. Leal, Margaret L. Gulley Tags: Review Source Type: research

Chromosomal Microarray Detection of Constitutional Copy Number Variation Using Saliva DNA
Chromosomal microarray (CMA) testing to detect copy number aberrations among individuals with multiple congenital anomalies and/or developmental delay is typically performed on peripheral blood DNA. However, the use of saliva DNA may be preferred for some patients, which prompted our validation study using six saliva DNA samples with a range of bacterial content (approximately 3% to 21%) and 20 paired blood and saliva specimens on the Agilent Technologies, Illumina, and Affymetrix CMA platforms. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - March 16, 2017 Category: Pathology Authors: Jennifer Reiner, Lisa Karger, Ninette Cohen, Lakshmi Mehta, Lisa Edelmann, Stuart A. Scott Tags: Regular Article Source Type: research

Detection of Aberrant TERT Promoter Methylation by Combined Bisulfite Restriction Enzyme Analysis for Cancer Diagnosis
Aberrant CpG dinucleotide methylation in a specific region of the telomerase reverse transcriptase (TERT) promoter is associated with increased TERT mRNA levels and malignancy in several cancer types. However, routine screening of this region to aid cancer diagnosis can be challenging because i) several established methylation assays may inaccurately report on hypermethylation of this particular region, ii) interpreting the results of methylation assays can sometimes be difficult for clinical laboratories, and iii) use of high-throughput methylation assays for a few patient samples can be cost prohibitive. (Source: Journal...
Source: Journal of Molecular Diagnostics - March 8, 2017 Category: Pathology Authors: Seungjae Lee, Sumit Borah, Armita Bahrami Tags: Technical Advance Source Type: research

Droplet Digital PCR Is a Reliable Tool for Monitoring Minimal Residual Disease in Acute Promyelocytic Leukemia
Nested PCR (nPCR) and real-time quantitative PCR (qPCR) are well-established methods for monitoring minimal residual disease (MRD) in acute promyelocytic leukemia (APL). Despite their remarkable sensitivity and specificity, both methods have inherent limitations, such as qualitative MRD evaluation and relative quantification. Herein, we used droplet digital PCR (ddPCR) to monitor MRD in 21 APL patients and compared its performance with nPCR and qPCR. After assessing the limit of detection (LOD) for each technique on serial dilutions of PML-RARA bcr1 and bcr3 transcripts, a total of 48 follow-up samples were analyzed and th...
Source: Journal of Molecular Diagnostics - March 4, 2017 Category: Pathology Authors: Claudia Brunetti, Luisa Anelli, Antonella Zagaria, Angela Minervini, Crescenzio F. Minervini, Paola Casieri, Nicoletta Coccaro, Cosimo Cumbo, Giuseppina Tota, Luciana Impera, Paola Orsini, Giorgina Specchia, Francesco Albano Tags: Regular Article Source Type: research

Abstracts of the 1st Global Congress on Molecular Pathology
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - March 1, 2017 Category: Pathology Source Type: research

Author Index
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - March 1, 2017 Category: Pathology Source Type: research

Correction
In the article entitled, “Next-Generation Assessment of Human Growth Factor Receptor 2 (ERBB2) Amplification Status Clinical Validation in the Context of a Hybrid Capture-Based, Comprehensive Solid Tumor Genomic Profiling Assay” (Volume 19, pages 244–254), which appeared in the March 2017 issue, the title contained er rors that were inadvertently introduced by the editorial office during the proof process. The correct title is “Next-Generation Assessment of Human Epithelial Growth Factor Receptor 2 (ERBB2) Amplification Status Clinical Validation in the Context of a Hybrid Capture-Based, C...
Source: Journal of Molecular Diagnostics - February 18, 2017 Category: Pathology Tags: Correction Source Type: research

Detection of Mycobacterium chelonae, Mycobacterium abscessus Group, and Mycobacterium fortuitum Complex by a Multiplex Real-Time PCR Directly from Clinical Samples Using the BD MAX System
A new multiplex PCR test was designed to detect Mycobacterium chelonae, Mycobacterium abscessus group, and Mycobacterium fortuitum complex on the BD MAX System. A total of 197 clinical samples previously submitted for mycobacterial culture were tested using the new protocol. Samples were first treated with proteinase K, and then each sample was inoculated into the BD MAX Sample Buffer Tube. Extraction and multiplex PCR were performed by the BD MAX System, using the BD MAX ExK TNA-3 extraction kit and BD TNA Master Mix, along with specific in-house designed primers and probes for each target. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 10, 2017 Category: Pathology Authors: Talita T. Rocchetti, Suzane Silbert, Alicia Gostnell, Carly Kubasek, Antonio C. Campos Pignatari, Raymond Widen Tags: Regular article Source Type: research

Guidelines for Colorectal Cancer Testing
This Editorial provides readers additional insight on the colorectal guideline appearing in this issue. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 10, 2017 Category: Pathology Authors: Barbara Zehnbauer, Robyn Temple-Smolkin, Federico A. Monzon Tags: Editorial Source Type: research

Reviewer Acknowledgment
The Editors gratefully acknowledge the generous assistance of the following reviewers who served The Journal of Molecular Diagnostics between January 1 and December 31,  2016. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 10, 2017 Category: Pathology Tags: Reviewer acknowledgment Source Type: research

Correction
In the article entitled, “The Clinical Implications of Inconsistently Methylated Results from Glioblastoma MGMT Testing by Replicate Methylation-Specific PCR” (Volume 18, pages 864–871 of the November 2016 issue of The Journal of Molecular Diagnostics; http://dx.doi.org/10.1016/j.jmoldx.2016.06.009), the authors infor med the editorial office of the following errors; on page 865, author N.L. is noted as the corresponding author and should be noted as the senior author. On page 867, “iii) year of diagnosis, age, and MGMT methylation status” should have been deleted from the following paragraph:...
Source: Journal of Molecular Diagnostics - February 10, 2017 Category: Pathology Tags: Correction Source Type: research

Editorial Board
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 10, 2017 Category: Pathology Source Type: research

Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 10, 2017 Category: Pathology Source Type: research

Instructions to Authors
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 10, 2017 Category: Pathology Source Type: research

Scientific Integrity Policy
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 10, 2017 Category: Pathology Source Type: research

Precision Medicine Requires Precision Laboratories
This commentary highlights the validation study by Lih et  al that supports the use of precision medicine for improved clinical trials. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - January 24, 2017 Category: Pathology Authors: Mangalathu S. Rajeevan, Tengguo Li, Elizabeth R. Unger Tags: Commentary Source Type: research

Application of Nuclear Magnetic Resonance to Detect Toxigenic Clostridium difficile from Stool Specimens
We evaluated the performance of an early prototype core molecular mirroring nuclear magnetic resonance detection platform (Mentor-100) to detect toxigenic Clostridium difficile from stool. This technology uses customized nanoparticles bound to target specific oligonucleotide probes that form binaries in the presence of nucleic acid from the target microorganism. Liquid patient stool specimens were seeded with C. difficile or other Clostridium species to determine the analytical sensitivity and specificity. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - January 9, 2017 Category: Pathology Authors: Paul Yang, Sara Hash, Katherine Park, Charlene Wong, Loganathan Doraisamy, Jonas Petterson, Cathy A. Petti, Pamela M. Ward, Seung H. Lee, Suresh Menon, Rosemary C. She Tags: Technical Advance Source Type: research

Targeted Next-Generation Sequencing in Molecular Subtyping of Lower-Grade Diffuse Gliomas
The 2007 World Health Organization Classification of Tumours of the Central Nervous System classifies lower-grade gliomas [LGGs (grades II to III diffuse gliomas)] morphologically as astrocytomas or oligodendrogliomas, and tumors with unclear ambiguous morphology as oligoastrocytomas. The World Health Organization's newly released (2016) classification incorporates molecular data. A single, targeted next-generation sequencing (NGS) panel was used for detecting single-nucleotide variation and copy number variation in 50 LGG cases originally classified using the 2007 criteria, including 36 oligoastrocytomas, 11 oligodendrogl...
Source: Journal of Molecular Diagnostics - December 31, 2016 Category: Pathology Authors: Jamal H. Carter, Samantha N. McNulty, Patrick J. Cimino, Catherine E. Cottrell, Jonathan W. Heusel, Katinka A. Vigh-Conrad, Eric J. Duncavage Tags: Regular Article Source Type: research

Development and Validation of a Preanalytic Procedure for Performing the cobas HPV Test in SurePath Preservative Fluid
The formation of chemical cross-links between nucleic acids and proteins in formalin-containing media presents challenges for human papillomavirus (HPV) testing of cervical samples collected in SurePath Preservative Fluid. A preanalytic process involving addition of a nucleophilic buffer and heating the sample to 120 °C was developed to reverse the effects of cross-linking and improve nucleic acid accessibility for the cobas HPV Test in SurePath. Cycle threshold (CT) values for cobas HPV detection were evaluated over time and various temperatures, and mean CT differences between pretreated and both untreated Su rePath ...
Source: Journal of Molecular Diagnostics - December 30, 2016 Category: Pathology Authors: Mark D. Krevolin, David Hardy, Jim Pane, Shagufta Aslam, Catherine M. Behrens Tags: Regular Article Source Type: research

The Effect of Nucleic Acid Extraction Platforms and Sample Storage on the Integrity of Viral RNA for Use in Whole Genome Sequencing
This study examined the fitness of one manual and four automated RNA extraction platforms commonly used in diagnostic laboratories for use in metagenomic sequencing, how the practice of storing sample material in Qiagen buffer AVL before extraction affected the integrity of viral RNA and its suitability for use in amplicon-based WGS methods, and how the addition of Triton X-100 to buffer AVL affected the capability of the extraction platforms and the integrity of viral RNA in stored samples. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 30, 2016 Category: Pathology Authors: Kuiama Lewandowski, Andrew Bell, Rory Miles, Simon Carne, David Wooldridge, Carmen Manso, Nicola Hennessy, Daniel Bailey, Steven T. Pullan, Saheer Gharbia, Richard Vipond Tags: Regular Article Source Type: research

Next-Generation Assessment of Human Epidermal Growth Factor Receptor 2 (ERBB2) Amplification Status
Establishing ERBB2 [human epidermal growth factor receptor 2 (HER2)] amplification status in breast and gastric carcinomas is essential to treatment selection. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) constitute the current standard for assessment. With further advancements in genomic medicine, new clinically relevant biomarkers are rapidly emerging and options for targeted therapy are increasing in patients with advanced disease, driving the need for comprehensive molecular profiling. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 24, 2016 Category: Pathology Authors: Dara S. Ross, Ahmet Zehir, Donavan T. Cheng, Ryma Benayed, Khedoudja Nafa, Jaclyn F. Hechtman, Yelena Y. Janjigian, Britta Weigelt, Pedram Razavi, David M. Hyman, Jos é Baselga, Michael F. Berger, Marc Ladanyi, Maria E. Arcila Tags: Regular article Source Type: research

Next-Generation Assessment of Human Epithelial Growth Factor Receptor 2 (ERBB2) Amplification Status
Establishing ERBB2 [human epidermal growth factor receptor 2 (HER2)] amplification status in breast and gastric carcinomas is essential to treatment selection. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) constitute the current standard for assessment. With further advancements in genomic medicine, new clinically relevant biomarkers are rapidly emerging and options for targeted therapy are increasing in patients with advanced disease, driving the need for comprehensive molecular profiling. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 24, 2016 Category: Pathology Authors: Dara S. Ross, Ahmet Zehir, Donavan T. Cheng, Ryma Benayed, Khedoudja Nafa, Jaclyn F. Hechtman, Yelena Y. Janjigian, Britta Weigelt, Pedram Razavi, David M. Hyman, Jos é Baselga, Michael F. Berger, Marc Ladanyi, Maria E. Arcila Tags: Regular article Source Type: research

Next-Generation Assessment of Human Growth Factor Receptor 2 (ERBB2) Amplification Status
Establishing ERBB2 [human epidermal growth factor receptor 2 (HER2)] amplification status in breast and gastric carcinomas is essential to treatment selection. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) constitute the current standard for assessment. With further advancements in genomic medicine, new clinically relevant biomarkers are rapidly emerging and options for targeted therapy are increasing in patients with advanced disease, driving the need for comprehensive molecular profiling. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 24, 2016 Category: Pathology Authors: Dara S. Ross, Ahmet Zehir, Donavan T. Cheng, Ryma Benayed, Khedoudja Nafa, Jaclyn F. Hechtman, Yelena Y. Janjigian, Britta Weigelt, Pedram Razavi, David M. Hyman, Jos é Baselga, Michael F. Berger, Marc Ladanyi, Maria E. Arcila Tags: Regular article Source Type: research

Next-Generation Assessment of ERBB2 Amplification Status
Establishing ERBB2 [human epidermal growth factor receptor 2 (HER2)] amplification status in breast and gastric carcinomas is essential to treatment selection. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) constitute the current standard for assessment. With further advancements in genomic medicine, new clinically relevant biomarkers are rapidly emerging and options for targeted therapy are increasing in patients with advanced disease, driving the need for comprehensive molecular profiling. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 24, 2016 Category: Pathology Authors: Dara S. Ross, Ahmet Zehir, Donavan T. Cheng, Ryma Benayed, Khedoudja Nafa, Jaclyn F. Hechtman, Yelena Y. Janjigian, Britta Weigelt, Pedram Razavi, David M. Hyman, Jos é Baselga, Michael F. Berger, Marc Ladanyi, Maria E. Arcila Tags: Regular Article Source Type: research

Next-Generation Assessment of ERBB2 (Human  Epidermal Growth Factor Receptor 2) Amplification Status
Establishing ERBB2 [human epidermal growth factor receptor 2 (HER2)] amplification status in breast and gastric carcinomas is essential to patients' treatment plans. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) constitute the current standard for assessment. With further advancements in genomic medicine, new clinically relevant biomarkers are rapidly emerging and options for targeted therapy are increasing in patients with advanced disease, driving the need for comprehensive molecular profiling. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 24, 2016 Category: Pathology Authors: Dara S. Ross, Ahmet Zehir, Donavan T. Cheng, Ryma Benayed, Khedoudja Nafa, Jaclyn F. Hechtman, Yelena Y. Janjigian, Britta Weigelt, Pedram Razavi, David M. Hyman, Jos é Baselga, Michael F. Berger, Marc Ladanyi, Maria E. Arcila Tags: Regular Article Source Type: research