Optimal reference gene selection for expression studies in human reticulocytes
This study aimed at selecting optimal reference genes for gene-expression analysis of reticulocytes and validating them in hereditary spherocytosis (HS) and β-thalassemia intermedia (βTI) patients. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 20, 2018 Category: Pathology Authors: Anu Aggarwal, Manu Jamwal, Ganesh Kumar V, Prashant Sharma, Man Updesh Singh Sachdeva, Deepak Bansal, Pankaj Malhotra, Reena Das Tags: Regular Article Source Type: research

Deciphering Elevated Microsatellite Alterations at Selected Tetra/Pentanucleotide Repeats, Microsatellite Instability, and Loss of Heterozygosity in Colorectal Cancers
Elevated microsatellite alterations at selected tetranucleotide repeats are common in colorectal cancers (CRCs). Its association with classic mono/dinucleotide microsatellite instability (MSI) is unknown. We assessed the stability of 13 tetranucleotide and three pentanucleotide repeat markers on both tumor and normal tissue from a cohort of 22 MSI-high (MSI-H) and 107 microsatellite stable (MSS) CRCs. When present, instability was observed at tetra/pentanucleotide repeats and defined as elevated microsatellite alterations at selected tetra/pentanucleotide repeats-high (EMASTP-H) ( ≥ 30% instability), EMASTP-low ( (Sourc...
Source: Journal of Molecular Diagnostics - February 20, 2018 Category: Pathology Authors: Yang Wang, Cindy L. Vnencak-Jones, Justin M. Cates, Chanjuan Shi Tags: Regular Article Source Type: research

Recommendations for Clinical CYP2C19 Genotyping Allele Selection: A Report of the Association for Molecular Pathology
This document was developed by the Pharmacogenetics (PGx) Working Group of the Association for Molecular Pathology (AMP) Clinical Practice Committee, whose aim is to recommend variants for inclusion in clinical pharmacogenetic testing panels. The goals of the AMP PGx Working Group are to define the key attributes of PGx alleles recommended for clinical testing, and to define a minimum set of variants that should be included in clinical PGx genotyping assays. These recommendations include a minimum panel of variant alleles (Tier 1) and an extended panel of variant alleles (Tier 2) that will aid clinical laboratories when de...
Source: Journal of Molecular Diagnostics - February 20, 2018 Category: Pathology Authors: Victoria M. Pratt, Andria L. Del Tredici, Houda Hachad, Yuan Ji, Lisa V. Kalman, Stuart A. Scott, Karen E. Weck Tags: Special Article Source Type: research

Chimerism analysis in the pediatric setting – Direct PCR from bone marrow, whole-blood, and cell fractions
Certain blood components and anticoagulants interfere with the PCR process and subsequent analysis. Here we demonstrate that reliable test results can be obtained for chimerism analysis despite omitting a DNA extraction step and performing PCR and fragment analysis directly on bone marrow, whole-blood, and individual cell fractions. For chimerism analysis, this is possible with the use of a robust commercially available PCR mix containing a DNA polymerase capable of DNA amplification directly from the sample without the need for pre-treatment. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 20, 2018 Category: Pathology Authors: Susanne Kricke, Lana Mhaldien, Rozendo Fernandes, Charizel Villanueva, Alistair Shaw, Paul Veys, Stuart Adams Tags: Regular Article Source Type: research

Reference Size Matching, Whole-Genome Amplification, and Fluorescent Labeling as a Method for Chromosomal Microarray Analysis of Clinically Actionable Copy Number Alterations in Formalin-Fixed, Paraffin-Embedded Tumor Tissue
Cancer genome copy number alterations (CNAs) assist clinicians in selecting targeted therapeutics. Solid tumor CNAs are most commonly evaluated in formalin-fixed, paraffin-embedded (FFPE) tissue by fluorescence in situ hybridization. Although fluorescence in situ hybridization is a sensitive and specific assay for interrogating preselected genomic regions, it provides no information about coexisting clinically significant copy number changes. Chromosomal microarray analysis is an alternative DNA-based method for interrogating genome-wide CNAs in solid tumors. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 19, 2018 Category: Pathology Authors: Shelly R. Gunn, Shailin Govender, Cynthe L. Sims, Aditi Khurana, Samuel Koo, Jayne Scoggin, Mathew W. Moore, Philip D. Cotter Tags: Technical advance Source Type: research

Evaluation of Two Commercial Real-Time PCR Kits for Aspergillus DNA Detection in Bronchoalveolar Lavage Fluid in Patients with Invasive Pulmonary Aspergillosis
Invasive pulmonary aspergillosis (IPA) is a common complication of immunosuppression. Rapid diagnosis using molecular techniques is essential to improve patient survival. PCR techniques are promising in enhancing Aspergillus detection in blood and respiratory samples. We evaluate for the first time the performances of two commercial real-time PCR kits, the A. fumigatus Bio-Evolution and the MycoGENIE A. fumigatus for the detection of A. fumigatus DNA in bronchoalveolar lavage (BAL) from patients with and without IPA. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 19, 2018 Category: Pathology Authors: Julie Denis, Faezeh Forouzanfar, Raoul Herbrecht, Elise Toussaint, Romain Kessler, Marcela Sabou, Ermanno Candolfi, Val érie Letsher-Bru Tags: Regular article Source Type: research

Reference size-matching, whole-genome amplification, and fluorescent labeling as a method for chromosomal microarray analysis of clinically actionable copy number alterations in formalin-fixed, paraffin-embedded tumor tissue
Cancer genome copy number alterations (CNAs) assist clinicians in selecting targeted therapeutics. Solid tumor CNAs are most commonly evaluated in formalin-fixed, paraffin-embedded (FFPE) tissue by fluorescence in situ hybridization. Although fluorescence in situ hybridization is a sensitive and specific assay for interrogating pre-selected genomic regions, it provides no information about co-existing clinically significant copy number changes. Chromosomal microarray analysis is an alternative DNA-based method for interrogating genome-wide CNAs in solid tumors. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 19, 2018 Category: Pathology Authors: Shelly R. Gunn, Shailin Govender, Cynthe L. Sims, Aditi Khurana, Samuel Koo, Jayne Scoggin, Mathew W. Moore, Philip D. Cotter Tags: Technical Advance Source Type: research

Evaluation of two commercial Real-Time PCR kits, A. fumigatus ® Bio-Evolution and MycoGENIE® A. fumigatus for Aspergillus DNA detection in Bronchoalveolar Lavage Fluid in patients with invasive pulmonary aspergillosis
Invasive pulmonary aspergillosis (IPA) is a common complication of immunosuppression. Rapid diagnosis using molecular techniques is essential to improve patient survival. PCR techniques are promising in enhancing Aspergillus detection in blood and respiratory samples. Here, we evaluate for the first time the performances of two commercial Real-Time PCR kits, the A. fumigatus ® Bio-Evolution and the MycoGENIE® A. fumigatus for the detection of A. fumigatus DNA in broncho-alveolar lavage (BAL) from patients with and without IPA. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 19, 2018 Category: Pathology Authors: Julie Denis, Faezeh Forouzanfar, Raoul Herbrecht, Elise Toussaint, Romain Kessler, Marcela Sabou, Ermanno Candolfi, Val érie Letsher-Bru Tags: Regular Article Source Type: research

Targeted Next-Generation Sequencing Is a Sensitive Tool for Differential Diagnosis of Myelodysplastic Syndromes in Bone Marrow Trephines
Myelodysplastic syndromes are hematological neoplasias in which immunohistological examination of bone-marrow trephines is important for a definite diagnosis. Unequivocal distinction from reactive bone-marrow changes is, however, sometimes difficult. As neoplastic clones in myelodysplastic syndrome carry mutations in recurrent genes, mutation detection by targeted next-generation sequencing may be a useful support for differential diagnosis. To elucidate the accuracy of this approach in the clinical diagnostic setting, we analyzed single and consecutive bone-marrow trephines processed for immunohistological examination fro...
Source: Journal of Molecular Diagnostics - February 19, 2018 Category: Pathology Authors: Andreas Br äuninger, Wolfgang Blau, Kristin Kunze, Ann-Kathrin Desch, Alexander Brobeil, Mehmet Kemal Tur, Benjamin Etschmann, Ulrich Günther, Dieter Körholz, Georg Schliesser, Andreas Käbisch, Michael Kiehl, Mathias Rummel, Stefan Gattenlöhner Tags: Regular article Source Type: research

Validation of a customized bioinformatics pipeline for a clinical next-generation sequencing test targeting solid tumor –associated variants
We present the validation of an open source tumor amplicon pipeline (OTA-pipeline) for clinical next-generation sequencing targeting solid tumor –associated variants. Raw data generated from 557 TruSight Tumor 26 samples as well as in silico data were analyzed by the OTA-pipeline and legacy pipeline and compared. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 19, 2018 Category: Pathology Authors: Thomas Schneider, Geoffrey H. Smith, Michael R. Rossi, Charles E. Hill, Linsheng Zhang Tags: Regular Article Source Type: research

Spinocerebellar Ataxia Tethering PCR
Spinocerebellar ataxia (SCA) types 1, 2, 3, 6, and 7, associated with a (CAG)n repeat expansion in coding sequences, are the most prevalent autosomal dominant ataxias worldwide (approximately 60% of the cases). In addition, the phenotype of SCA2 expansions has been now extended to Parkinson disease and amyotrophic lateral sclerosis. Their diagnosis is currently based on a PCR to identify small expanded alleles, followed by a second-level test whenever a false normal homozygous or a CAT interruption in SCA1 needs to be verified. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 17, 2018 Category: Pathology Authors: Claudia Cagnoli, Alessandro Brussino, Cecilia Mancini, Marina Ferrone, Laura Orsi, Paola Salmin, Patrizia Pappi, Elisa Giorgio, Elisa Pozzi, Simona Cavalieri, Eleonora Di Gregorio, Marta Ferrero, Alessandro Filla, Giuseppe De Michele, Cinzia Gellera, Cate Tags: Regular article Source Type: research

Rapid, Loop-Mediated Isothermal Amplification Detection of Celiac Disease Risk Alleles
Human leukocyte antigen (HLA) genotyping has become a useful investigation in the diagnostic work-up of celiac disease (CD), with utility in risk stratification and screening. However, broad application of this technology has been hindered by the cost and time burden of conventional laboratory-based assays. We have developed and validated CD –loop-mediated isothermal amplification (CD-LAMP), a LAMP assay, which enables rapid identification of the signature CD risk genotypes, HLA-DQ2.5, HLA-DQ8, HLA-DQ2.2, and HLA-DQA1*05. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 17, 2018 Category: Pathology Authors: Michael Erlichster, Jason A. Tye-Din, Michael D. Varney, Efstratios Skafidas, Patrick Kwan Tags: Regular article Source Type: research

SCA Tethering-PCR: A Rapid Genetic Test for the Diagnosis of SCA1 –3, 6, and 7 by PCR and Capillary Electrophoresis
Spinocerebellar ataxias (SCA) type 1, 2, 3, 6, and 7, associated with a (CAG)n repeat expansion in coding sequences, are the most prevalent autosomal dominant ataxias worldwide (approximately 60% of the cases). In addition, the phenotype of SCA2 expansions has been now extended to Parkinson's disease and amyotrophic lateral sclerosis. Their diagnosis is presently based on a PCR to identify small expanded alleles, followed by a second-level test whenever the suspect of false normal homozygous, or a CAT interruption in SCA1 needs to be verified. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 17, 2018 Category: Pathology Authors: Claudia Cagnoli, Alessandro Brussino, Cecilia Mancini, Marina Ferrone, Laura Orsi, Paola Salmin, Patrizia Pappi, Elisa Giorgio, Elisa Pozzi, Simona Cavalieri, Eleonora Di Gregorio, Marta Ferrero, Alessandro Filla, Giuseppe De Michele, Cinzia Gellera, Cate Tags: Regular article Source Type: research

Rapid, Loop-Mediated Isothermal Amplification Detection of Coeliac Disease Risk Alleles
Human leukocyte antigen (HLA) genotyping has become a useful investigation in the diagnostic work-up of coeliac disease (CD), with utility in risk stratification and screening. However, broad application of this technology has been hindered by the cost and time burden of conventional laboratory-based assays. We have developed and validated CD –loop-mediated isothermal amplification (CD-LAMP), a LAMP assay, which enables rapid identification of the signature CD risk genotypes, HLA-DQ2.5, HLA-DQ8, HLA-DQ2.2, and HLA-DQA1*05. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 17, 2018 Category: Pathology Authors: Michael Erlichster, Jason A. Tye-Din, Michael D. Varney, Efstratios Skafidas, Patrick Kwan Tags: Regular article Source Type: research

Assessment of Capture and Amplicon-Based Approaches for the Development of a Targeted Next-Generation Sequencing Pipeline to Personalize Lymphoma Management
Targeted next-generation sequencing panels are increasingly used to assess the value of gene mutations for clinical diagnostic purposes. For assay development, amplicon-based methods have been preferentially used on the basis of short preparation time and small DNA input amounts. However, capture sequencing has emerged as an alternative approach because of high testing accuracy. We compared capture hybridization and amplicon sequencing approaches using fresh-frozen and formalin-fixed, paraffin-embedded tumor samples from eight lymphoma patients. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 8, 2018 Category: Pathology Authors: Stacy S. Hung, Barbara Meissner, Elizabeth A. Chavez, Susana Ben-Neriah, Daisuke Ennishi, Martin R. Jones, Hennady P. Shulha, Fong Chun Chan, Merrill Boyle, Robert Kridel, Randy D. Gascoyne, Andrew J. Mungall, Marco A. Marra, David W. Scott, Joseph M. Con Tags: Regular articles Source Type: research

Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors
In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - January 23, 2018 Category: Pathology Authors: Neal I. Lindeman, Philip T. Cagle, Dara L. Aisner, Maria E. Arcila, Mary Beth Beasley, Eric Bernicker, Carol Colasacco, Sanja Dacic, Fred R. Hirsch, Keith Kerr, David J. Kwiatkowski, Marc Ladanyi, Jan A. Nowak, Lynette Sholl, Robyn Temple-Smolkin, Benjam Tags: Special Article Source Type: research

Next-Generation Sequencing for Lymphomas
This commentary highlights the article by Hung et  al that details the design and implementation of a 32-gene next-generation sequencing panel for lymphomas and compares hybrid-capture with amplicon-based next-generation sequencing approaches. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - January 19, 2018 Category: Pathology Authors: Robert S. Ohgami, Andreas Rosenwald, Adam Bagg Tags: Commentary Source Type: research

Keeping Practice Recommendations in Step with Advancing Knowledge
This editorial comments on the updated molecular testing guideline for lung cancer patients. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - January 19, 2018 Category: Pathology Authors: Barbara Zehnbauer Tags: Editorial Source Type: research

Next-Generation Sequencing for Lymphomas: Perfecting a Pipeline for Personalized Pathobiologic and Prognostic Predictions
This commentary highlights the article by Hung et al that details the design and implementation of a 32-gene next-generation sequencing (NGS) panel for lymphomas, and compares hybrid-capture versus amplicon-based NGS approaches. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - January 19, 2018 Category: Pathology Authors: Robert S. Ohgami, Andreas Rosenwald, Adam Bagg Tags: Commentary Source Type: research

Evaluation of a pan-Leishmania Spliced-Leader RNA Detection Method in Human Blood and Experimentally-Infected Syrian Golden Hamsters
This study compared the limits of detection of various real-time PCR assays in hamsters infected with Leishmania infantum, in spiked human blood and in clinical blood samples from visceral leishmaniasis patients. The SL-RNA assay showed an excellent analytical sensitivity in tissues (0.005 and 0.002 parasites per mg liver and spleen, respectively) and was not prone to false-positive reactions. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - January 17, 2018 Category: Pathology Authors: Eline Eberhardt, Magali Van den Kerkhof, Dimitri Bult é, Dorien Mabille, Lieselotte Van Bockstal, Séverine Monnerat, Fabiana Alves, Jane Mbui, Peter Delputte, Paul Cos, Sarah Hendrickx, Louis Maes, Guy Caljon Tags: Regular article Source Type: research

SNPitty
Exploration and visualization of next-generation sequencing data are crucial for clinical diagnostics. Software allowing simultaneous visualization of multiple regions of interest coupled with dynamic heuristic filtering of genetic aberrations is, however, lacking. Therefore, the authors developed the web application SNPitty that allows interactive visualization and interrogation of variant call format files by using B-allele frequencies of single-nucleotide polymorphisms and single-nucleotide variants, coverage metrics, and copy numbers analysis results. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - January 2, 2018 Category: Pathology Authors: Job van Riet, Niels M.G. Krol, Peggy N. Atmodimedjo, Erwin Brosens, Wilfred. F.J. van IJcken, Maurice P.H.M. Jansen, John W.M. Martens, Leendert H. Looijenga, Guido Jenster, Hendrikus J. Dubbink, Winand N.M. Dinjens, Harmen J.G. van de Werken Tags: Technical advance Source Type: research

Droplet Digital PCR for Mutation Detection in Formalin-Fixed, Paraffin-Embedded Melanoma Tissues
The identification of somatic mutations is crucial for guiding therapeutic decisions about personalized melanoma treatment. However, genetic analysis of tumors is usually performed on limited and often low-quality DNA from tumors with low tumor cellularity and high tumor heterogeneity. Different mutation-detection platforms exist, with varying analytical sensitivities. Here we evaluated the detection of common mutations in BRAF, NRAS, and TERT promoter in 40 melanoma FFPE tissues using Droplet Digital (dd)PCR, and compared the results to the detection rates obtained by Sanger sequencing and pyrosequencing. (Source: Journal...
Source: Journal of Molecular Diagnostics - January 2, 2018 Category: Pathology Authors: Ashleigh C. McEvoy, Benjamin A. Wood, Nima M. Ardakani, Michelle Pereira, Robert Pearce, Lester Cowell, Cleo Robinson, Fabienne Grieu-Iacopetta, Alexander J. Spicer, Benhur Amanuel, Melanie Ziman, Elin S. Gray Tags: Regular article Source Type: research

SNPitty: An intuitive web-application for interactive B-allele frequency and copy-number visualization of next-generation sequencing data
Exploration and visualization of next-generation sequencing data is crucial for clinical diagnostics. Software allowing simultaneous visualization of multiple regions-of-interest coupled with dynamic heuristic filtering of genetic aberrations is however lacking. Therefore, we developed the web-application SNPitty that allows interactive visualization and interrogation of variant call format (VCF) files by utilizing B-allele frequencies of single nucleotide polymorphisms and single nucleotide variants, coverage metrics and copy-numbers analysis results. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - January 2, 2018 Category: Pathology Authors: Job van Riet, Niels M.G. Krol, Peggy N. Atmodimedjo, Erwin Brosens, Wilfred. F.J. van IJcken, Maurice P.H.M. Jansen, John W.M. Martens, Leendert H. Looijenga, Guido Jenster, Hendrikus J. Dubbink, Winand N.M. Dinjens, Harmen J.G. van de Werken Tags: Technical Advance Source Type: research

Droplet Digital PCR for Mutation Detection in Formalin-Fixed, Paraffin-Embedded Melanoma Tissues: A Comparison with Sanger Sequencing and Pyrosequencing
Identification of somatic mutations is crucial to guide therapeutic decisions for personalized melanoma treatment. However, genetic analysis of the tumor is usually performed on limited and often low-quality DNA, from tumors with low tumor cellularity and high tumor heterogeneity. Different mutation detection platforms exist with varying analytical sensitivities. Here we evaluated the detection of common mutations in BRAF, NRAS, and TERT-promoter in 40 melanoma formalin-fixed, paraffin-embedded tissues using droplet digital PCR (ddPCR), and compared the results to the detection rate obtained by Sanger sequencing and pyrose...
Source: Journal of Molecular Diagnostics - January 2, 2018 Category: Pathology Authors: Ashleigh C. McEvoy, Benjamin A. Wood, Nima M. Ardakani, Michelle Pereira, Robert Pearce, Lester Cowell, Cleo Robinson, Fabienne Grieu-Iacopetta, Alexander J. Spicer, Benhur Amanuel, Melanie Ziman, Elin S. Gray Tags: Regular Article Source Type: research

Evaluation of Diagnostic Utility of a High-Risk Human Papillomavirus PCR Test on Formalin-Fixed, Paraffin-Embedded Head and Neck Tumor Tissues
The increasing prevalence of high-risk human papillomavirus (HR-HPV) –associated head and neck squamous cell carcinoma (HNSCC) has prompted strong clinical demands for detecting HR-HPV directly in the tumor. Although p16 immunohistochemistry (IHC) has been the standard testing method, it has limitations including false positivity, lack of sensitivity in low tumor c ell samples such as fine-needle aspirate (FNA), and its subjectivity. We developed a modified method based on the Roche Cobas 4800 HR-HPV PCR assay and evaluated the performance characteristics and the diagnostic utility of this assay for direct HR-HPV det...
Source: Journal of Molecular Diagnostics - December 19, 2017 Category: Pathology Authors: Albert Njoroge Huho, Nour Yadak, Th èrése Jeanne Bocklage, Shangxin Yang Tags: Regular article Source Type: research

A Novel and Reliable Method to Detect Microsatellite Instability in Colorectal Cancer by Next-Generation Sequencing
Two types of molecular tests have been established to assess the deficiency of DNA mismatch repair (MMR) system: microsatellite instability (MSI) and immunohistochemical (IHC) analysis. We have developed a reliable method to analyze the MSI status by next-generation sequencing (NGS) based on read count distribution. A total of 91 patients with primary colorectal cancer were recruited. These patients included 54 cases with the loss of expression of any MMR protein in IHC suggesting deficient MMR (dMMR), and 37 cases of colorectal cancer with staining of all four MMR proteins in IHC, suggesting proficient MMR (pMMR) in posto...
Source: Journal of Molecular Diagnostics - December 19, 2017 Category: Pathology Authors: Lizhen Zhu, Yanqin Huang, Xuefeng Fang, Chenglin Liu, Wanglong Deng, Chenhan Zhong, Jinghong Xu, Dong Xu, Ying Yuan Tags: Regular article Source Type: research

Evaluation of Diagnostic Utility of a High-Risk Human Papillomavirus PCR Test on Formalin Fixed, Paraffin-Embedded Head and Neck Tumor Tissues
The increasing prevalence of high-risk human papillomavirus (HR-HPV) –associated head and neck squamous cell carcinoma (HNSCC) has prompted strong clinical demands for detecting HR-HPV directly in the tumor. Although p16 immunohistochemistry (IHC) has been the standard testing method, it has limitations including false positivity, lack of sensitivity in low tumor c ell samples such as fine needle aspirate (FNA), and its subjectivity. We developed a modified method based on the Roche Cobas 4800 HR-HPV PCR assay and evaluated the performance characteristics and the diagnostic utility of this assay for direct HR-HPV det...
Source: Journal of Molecular Diagnostics - December 19, 2017 Category: Pathology Authors: Albert Njoroge Huho, Nour Yadak, Th èrése Jeanne Bocklage, Shangxin Yang Tags: Regular Article Source Type: research

Evaluation of a Urine-Based Rapid Molecular Diagnostic Test with Potential to be used at Point-of-Care for Pulmonary Tuberculosis: Cape Town Cohort
In this study, a new urine-based Tr-DNA molecular assay was evaluated for diagnosis of pulmonary tuberculosis among 428 adult pulmonary TB suspects (164 HIV-positive, 263 HIV-negative) from Cape Town, South Africa. Tr-DNA was isolated from 4 mL EDTA urine, and rapid double-stranded primer-based PCR method performed targeting Mycobacterium tuberculosis–specific direct repeat region. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 18, 2017 Category: Pathology Authors: Krutarth Patel, Matilde Nagel, Maria Wesolowski, Stefan Dees, Eric Rivera-Milla, Christof Geldmacher, Keertan Dheda, Michael Hoelscher, Ines Labugger Tags: Regular Article Source Type: research

Comprehensive Genomic Profiling of Malignant Effusions in Patients with Metastatic Lung Adenocarcinoma
Cytology samples are being increasingly utilized for comprehensive molecular testing. Although fine-needle aspirates are adequate substrates for high-throughput sequencing, the suitability of malignant body fluids remains largely unexplored. Herein, we investigated the adequacy and utility of performing targeted next-generation sequencing (NGS) on malignant effusions from patients with metastatic lung adenocarcinoma. Thirty-two effusion samples that were submitted for hybrid capture –based NGS using a clinically validated solid tumor genotyping panel were examined. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 18, 2017 Category: Pathology Authors: Soo-Ryum Yang, Chieh-Yu Lin, Henning Stehr, Steven R. Long, Christina S. Kong, Gerald J. Berry, James L. Zehnder, Christian A. Kunder Tags: Regular Article Source Type: research

Conventional and single-molecule targeted sequencing method for specific variant detection in IKBKG whilst bypassing the IKBKGP1 pseudogene
In addition to Sanger sequencing, next-generation sequencing of gene panels and exomes has emerged as a standard diagnostic tool in many laboratories. However, these captures can miss regions, have poor efficiency, or capture pseudogenes which hamper proper diagnoses. One such example is the primary immunodeficiency –associated gene IKBKG. Its pseudogene IKBKGP1 makes traditional capture methods aspecific. We therefore developed a long-range PCR method to efficiently target IKBKG, as well as two associated genes (IRAK4 and MYD88), whilst bypassing the IKBKGP1 pseudogene. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 18, 2017 Category: Pathology Authors: Glynis Frans, Wim Meert, Jutte Van der Werff Ten Bosch, Isabelle Meyts, Xavier Bossuyt, Joris R. Vermeesch, Matthew S. Hestand Tags: Regular Article Source Type: research

The history and impact of molecular coding changes on coverage and reimbursement of molecular diagnostic tests: transition from stacking codes to the current molecular code set including genomic sequencing procedures
Changes in coding and coverage create uncertain reimbursement environment for molecular pathology laboratories. We analyzed our experience with two representative molecular oncology tests: a T-cell receptor (TCR) beta rearrangement test and a large (467 gene) cancer next-generation sequencing panel the Columbia Combined Cancer Panel, CCCP. Prior to 2013, the TCR beta test was coded using “stacked” current procedural terminology codes and subsequently transitioned to a tier 1 code. CCCP was coded using a combination of tier 1 and 2 codes until 2015, when a new Genomic Sequencing Procedure code was adopted. (Sour...
Source: Journal of Molecular Diagnostics - December 18, 2017 Category: Pathology Authors: Susan J. Hsiao, Mahesh M. Mansukhani, Melissa C. Carter, Anthony N. Sireci Tags: Regular Article Source Type: research

Identification of Germline Variants in Tumor Genomic Sequencing Analysis
This Correspondence relates to the article by Li et  al (Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and the College of American Pathologists. J Mol Diagn 2017, 19:4–23). (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 14, 2017 Category: Pathology Authors: Nathan D. Montgomery, Sara R. Selitsky, Nirali M. Patel, D. Neil Hayes, Joel S. Parker, Karen E. Weck Tags: Correspondence Source Type: research

Navigating the Peer Review Process
This editorial provides insights and guidelines for publishing in The Journal of Molecular Diagnostics. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 14, 2017 Category: Pathology Authors: Barbara Zehnbauer, Emily H. Essex, Chhavi Chauhan Tags: Editorial Source Type: research

Authors' Reply
to the Letter to the Editor by Montgomery et  al (Identification of Germline Variants in Tumor Genomic Sequencing Analysis. J Mol Diagn 2017, 19:XXXX–XXXX). (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 14, 2017 Category: Pathology Authors: Marilyn M. Li, Michael Datto, Eric J. Duncavage, Shashikant Kulkarni, Neal I. Lindeman, Somak Roy, Apostolia M. Tsimberidou, Cindy L. Vnencak-Jones, Daynna J. Wolff, Anas Younes, Marina N. Nikiforova Tags: Correspondence Source Type: research

Editorial Board
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 14, 2017 Category: Pathology Source Type: research

Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 14, 2017 Category: Pathology Source Type: research

Instructions to Authors
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 14, 2017 Category: Pathology Source Type: research

Scientific Integrity Policy
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 14, 2017 Category: Pathology Source Type: research

Simple Detection of Telomere Fusions in Pancreatic Cancer, Intraductal Papillary Mucinous Neoplasm, and Pancreatic Cyst Fluid
Telomere end-to-end fusions are an important source of chromosomal instability that arise in cells with critically shortened telomeres. We developed a nested real-time quantitative PCR method for telomere fusion detection in pancreatic ductal adenocarcinomas, intraductal papillary mucinous neoplasms (IPMNs), and IPMN cyst fluids. Ninety-one pancreatic cancer cell lines and xenograft samples, 93 IPMNs, and 93 surgically aspirated IPMN cyst fluid samples were analyzed. The association between telomere shortening, telomerase activity, and telomere fusion detection was evaluated. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 8, 2017 Category: Pathology Authors: Tatsuo Hata, Marco Dal Molin, Anne McGregor-Das, Tae Jun Song, Christopher Wolfgang, James R. Eshleman, Ralph H. Hruban, Michael Goggins Tags: Regular article Source Type: research

Telomere Diagnostics for Pancreatic Neoplasms and Cysts
This commentary highlights the article by Hata et  al that examines markers for assessing neoplastic progression. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 15, 2017 Category: Pathology Authors: Loren Joseph Tags: Commentary Source Type: research

Is Tubulocystic Renal Cell Carcinoma Real?
This commentary highlights the article by Lawrie et  al that validates that tubulocystic renal cell carcinoma is a distinct type of renal neoplasm. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 15, 2017 Category: Pathology Authors: Yi Ding, Hiroshi Miyamoto, Paul G. Rothberg Tags: Commentary Source Type: research

Commentary: Telomere Diagnostics for Pancreatic Neoplasms and Cysts
Advances in imaging of the pancreas have led to a dramatic increase in the frequency of presymptomatic detection of lesions. This is especially problematic because of the difficulty in sampling pancreatic lesions, the morbidity in resecting even small lesions, and the dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) despite early detection. Although some lesions have both a solid and a cystic component, frequently only a cyst is present. The majority of lesions found incidentally do not represent PDAC, but several classes of neoplasms have an increased risk of progression to PDAC. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 15, 2017 Category: Pathology Authors: Loren Joseph Tags: Commentary Source Type: research

Is Tubulocystic Renal Cell Carcinoma Real? Genomic Analysis Confirms the WHO Classification
This commentary highlights the article by Lawrie et al that validates that tubulocystic renal cell carcinoma is a distinct type of renal neoplasm. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 15, 2017 Category: Pathology Authors: Yi Ding, Hiroshi Miyamoto, Paul G. Rothberg Tags: Commentary Source Type: research

Standards and Guidelines for Validating Next-Generation Sequencing Bioinformatics Pipelines
Bioinformatics pipelines are an integral component of next-generation sequencing (NGS). Processing raw sequence data to detect genomic alterations has significant impact on disease management and patient care. Because of the lack of published guidance, there is currently a high degree of variability in how members of the global molecular genetics and pathology community establish and validate bioinformatics pipelines. Improperly developed, validated, and/or monitored pipelines may generate inaccurate results that may have negative consequences for patient care. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 14, 2017 Category: Pathology Authors: Somak Roy, Christopher Coldren, Arivarasan Karunamurthy, Nefize S. Kip, Eric W. Klee, Stephen E. Lincoln, Annette Leon, Mrudula Pullambhatla, Robyn L. Temple-Smolkin, Karl V. Voelkerding, Chen Wang, Alexis B. Carter Tags: Special article Source Type: research

Standards and Guidelines for Validating Next-Generation Sequencing Bioinformatics Pipelines: A Joint Recommendation of the Association for Molecular Pathology and College of American Pathologists
Bioinformatics pipelines are an integral component of next-generation sequencing (NGS). Processing raw sequence data to detect genomic alterations has significant impact on disease management and patient care. Due to the lack of published guidance, there is currently a high degree of variability in how members of the global molecular genetics and pathology community establish and validate bioinformatics pipelines. Improperly developed, validated, and/or monitored pipelines may generate inaccurate results that may have negative consequences for patient care. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 14, 2017 Category: Pathology Authors: Somak Roy, Christopher Coldren, Arivarasan Karunamurthy, Nefize Sertac Kip, Eric W. Klee, Stephen E. Lincoln, Annette Leon, Mrudula Pullambhatla, Robyn L. Temple-Smolkin, Karl V. Voelkerding, Chen Wang, Alexis B. Carter Tags: Special Article Source Type: research

Development and Evaluation of a Pan-Sarcoma Fusion Gene Detection Assay Using the NanoString nCounter Platform
The NanoString nCounter assay is a high-throughput hybridization technique using target-specific probes that can be customized to test for numerous fusion transcripts in a single assay utilizing RNA from formalin-fixed, paraffin-embedded material. We designed a NanoString assay targeting 174 unique fusion junctions in 25 sarcoma types. The study cohort comprised 212 cases, 96 of which showed fusion gene expression by the NanoString assay, including all 20 Ewing sarcomas, 11 synovial sarcomas, and five myxoid liposarcomas tested. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 2, 2017 Category: Pathology Authors: Kenneth Tou En Chang, Angela Goytain, Tracy Tucker, Aly Karsan, Cheng-Han Lee, Torsten O. Nielsen, Tony L. Ng Tags: Regular article Source Type: research

Editorial Board
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 21, 2017 Category: Pathology Source Type: research

Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 21, 2017 Category: Pathology Source Type: research

Title Page
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 21, 2017 Category: Pathology Source Type: research

Disclosure Statement
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 21, 2017 Category: Pathology Source Type: research