Rapid Next-Generation Sequencing Method for Prediction of Prostate Cancer Risks
Publication date: Available online 12 December 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Viacheslav Y. Fofanov, Kinnari Upadhyay, Alexander Pearlman, Johnny Loke, Vivian O, Yongzhao Shao, Stephen Freedland, Harry OstrerProstate cancer is the most commonly diagnosed male cancer and the second leading cause of cancer deaths among men in the United States, with approximately 220,000 new diagnoses and approximately 27,000 deaths each year. Men with clinical low-risk disease can receive active surveillance to safely preserve quality of life, provided that the risk of an undetected aggressive cancer can be manag...
Source: The Journal of Molecular Diagnostics - December 12, 2018 Category: Pathology Source Type: research

Rapid and sensitive detection of azole-resistant Aspergillus fumigatus by tandem-repeat loop-mediated isothermal amplification
Publication date: Available online 4 December 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Ling-Shan Yu, Jesus Rodriguez-Manzano, Kenny Malpartida-Cardenas, Thomas Sewell, Oliver Bader, Darius Armstrong-James, Matthew C. Fisher, Pantelis GeorgiouAbstractInvasive human fungal infections caused by multi-azole resistant Aspergillus fumigatus are associated with increasing rates of mortality in susceptible patients. Current methods of diagnosing infections caused by multi-azole resistant A. fumigatus are, however, not well suited for use in clinical point-of-care testing or in the field. Loop-mediated isothermal ...
Source: The Journal of Molecular Diagnostics - December 5, 2018 Category: Pathology Source Type: research

Design, optimization, and multisite evaluation of a targeted next-generation sequencing assay system for chimeric RNAs from gene fusions and exon-skipping events in non–small-cell lung cancer
We describe the development and verification of a system for targeted RNA-Seq for the analysis of challenging, low-input solid tumor biopsies that includes reagents for nucleic acid quantification and library preparation, run controls, and companion bioinformatics software. Assay development reconciled sequence discrepancies in public databases, created predictive formalin-fixed, paraffin-embedded RNA qualification metrics, and eliminated read misidentification due to “index hopping” events on the next-generation sequencing flow cell. The optimized and standardized system was analytically verified internally an...
Source: The Journal of Molecular Diagnostics - December 5, 2018 Category: Pathology Source Type: research

Software-assisted manual review of clinical next-generation sequencing data An alternative to routine Sanger sequencing confirmation with equivalent results in >15,000 germline DNA screens
Publication date: Available online 4 December 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Dale Muzzey, Shera Kash, Jillian I. Johnson, Laura M. Melroy, Piotr Kaleta, Kelly A. Pierce, Kaylene Ready, Hyunseok P. Kang, Kevin R. HaasAbstractClinical genomic tests increasingly utilize a next-generation sequencing (NGS) platform due in part to the high fidelity of variant calls, yet rare errors are still possible. In germline DNA screening, failure to correct such errors could have serious consequences for patients, who may follow an unwarranted screening or surgical-management path. It has been suggested that rou...
Source: The Journal of Molecular Diagnostics - December 5, 2018 Category: Pathology Source Type: research

A Novel Multiplex droplet digital PCR Assay to Identify and Quantify KRAS Mutations in Clinical Specimens
Publication date: Available online 23 November 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Miguel Alcaide, Matthew Cheung, Kevin Bushell, Sarah E. Arthur, Hui-Li Wong, Joanna Karasinska, Daniel Renouf, David F. Schaeffer, Suzan McNamara, Mathilde Couetoux du Tertre, Gerald Batist, Hagen F. Kennecke, Aly Karsan, Ryan D. MorinRecurrent activating point mutations in KRAS are critical drivers in pancreatic cancer and have been attributed to resistance to anti–epidermal growth factor receptor therapy in colorectal cancer. Although KRAS genotyping provides limited clinical utility in the diagnosis and manage...
Source: The Journal of Molecular Diagnostics - November 23, 2018 Category: Pathology Source Type: research

Evaluation for Genetic Disorders in the Absence of a Clinical Indication for Testing: Elective Genomic Testing
Publication date: Available online 17 November 2018Source: The Journal of Molecular DiagnosticsAuthor(s): James T. Lu, Matthew Ferber, Jill Hagenkord, Elissa Levin, Sarah South, Hyunseok P. Kang, Kimberly A. Strong, David P. BickAbstractThe increasing quality and diminishing cost of next-generation sequencing has transformed our ability to interrogate large quantities of genetic information. This has led to a dramatic increase in the number of elective genomic tests performed. In this article elective test denotes a test that a patient chooses to undertake without a clinical indication. The variety of elective genomic test...
Source: The Journal of Molecular Diagnostics - November 17, 2018 Category: Pathology Source Type: research

Expedited Analysis and Reporting of Multiple Mutations that Modify Medical Management of Myeloid Malignancies: It's About (Turnaround) Time!
Publication date: Available online 19 October 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Michael J. Kluk, Adam Bagg (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - November 16, 2018 Category: Pathology Source Type: research

Diagnostic Targetd Sequencing Adjudication: Algorithms for Adjudicating Targeted Infectious Disease Next-Generation Sequencing Panels
Publication date: Available online 28 September 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Turner A. Conrad, Chien-Chi Lo, Jeffrey W. Koehler, Amanda S. Graham, Christopher P. Stefan, Adrienne T. Hall, Christina E. Douglas, Patrick S.G. Chain, Timothy D. MinogueNext-generation sequencing (NGS) for infectious disease diagnostics is a relatively new and underdeveloped concept. If this technology is to become a regulatory-grade clinical diagnostic, standardization in the form of locked-down assays and firmly established underlying processes is necessary. Targeted sequencing, specifically by amplification of ge...
Source: The Journal of Molecular Diagnostics - November 15, 2018 Category: Pathology Source Type: research

In Silico Mutator: In Silico MutatorSoftware for Bioinformatics Pipeline Validation of Clinical Next-Generation Sequencing Assays
Publication date: Available online 29 September 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Sushant A. Patil, Ibro Mujacic, Lauren L. Ritterhouse, Jeremy P. Segal, Sabah KadriLack of reliable reference samples containing different mutations of interest across large sets of disease-relevant loci limits the extensive validation clinical next-generation sequencing (NGS) assays and their associated bioinformatics pipelines. Herein, we have generated a publicly available, highly flexible tool, in silico Mutator (insiM), to introduce point mutations, insertions, deletions, and duplications of any size into real da...
Source: The Journal of Molecular Diagnostics - November 15, 2018 Category: Pathology Source Type: research

Screening for Regulatory Variants in 460 kb Encompassing the CFTR Locus in Cystic Fibrosis Patients
Publication date: Available online 5 October 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Jenny L. Kerschner, Sujana Ghosh, Alekh Paranjapye, Wilmel R. Cosme, Marie-Pierre Audrézet, Miyuki Nakakuki, Hiroshi Ishiguro, Claude Férec, Johanna Rommens, Ann HarrisIt is estimated that up to 5% of cystic fibrosis transmembrane conductance regulator (CFTR) pathogenic alleles are unidentified. Some of these errors may lie in noncoding regions of the locus and affect gene expression. To identify regulatory element variants in the CFTR locus, SureSelect-targeted enrichment of 460 kb encompassing the gene wa...
Source: The Journal of Molecular Diagnostics - November 15, 2018 Category: Pathology Source Type: research

Mutation burden and I index for Detection of microsatellite instability in colorectal cancer by targeted next-generation sequencing
Publication date: Available online 31 October 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Jeong Eun Kim, Sung-Min Chun, Yong Sang Hong, Kyu-pyo Kim, Sun Young Kim, Jihun Kim, Chang-Ohk Sung, Eun Jeong Cho, Tae Won Kim, Se Jin JangNext-generation sequencing (NGS) panels are widely used for defining tumor mutation profiles and determining treatment approaches. We performed targeted NGS with 382 genes in colorectal cancer with known microsatellite instability (MSI) status. After exclusion of germline alterations, load of somatic mutations and small insertion/deletion (indel) alterations were determined. In the ...
Source: The Journal of Molecular Diagnostics - October 31, 2018 Category: Pathology Source Type: research

Optimizing a Metatranscriptomic Next-Generation Sequencing Protocol for Bronchoalveolar Lavage Diagnostics
We describe here a RNA-based metatranscriptomic NGS (mtNGS) protocol for culture-independent detection of potential infectious pathogens, using clinical bronchoalveolar lavage specimens as an example. We present both an optimized workflow for experimental sequence data collection and a simplified pipeline for bioinformatics sequence data processing. As demonstrated, the whole protocol takes about 24 to 36 hours to detect a wide range of Gram-positive and -negative bacteria, and possibly other viral and/or fungal pathogens. In particular, we introduce a spike-in RNA mix as an internal control, which plays a critical role in...
Source: The Journal of Molecular Diagnostics - October 31, 2018 Category: Pathology Source Type: research

Development of novel mutation-specific droplet digital PCR assays detecting TERT promoter mutations in tumor and plasma samples
We describe the development of novel probe-based droplet digital PCR (ddPCR) assays that specifically detect and quantify these two mutations along with the less common 242-243 CC>TT mutation, and demonstrate their application using human tumor and plasma samples from melanoma patients. Assay designs and running conditions were optimized using cancer cell line genomic DNAs with the C228T or C250T mutations. The limit of detection (LOD) was 0.062% and 0.051% mutant allele fraction (MAF) for the C228T and C250T assays, respectively. One hundred percent concordance was observed between ddPCR and sequencing-based orthogonal...
Source: The Journal of Molecular Diagnostics - October 26, 2018 Category: Pathology Source Type: research

Clinical Evaluation of Massively Parallel RNA Sequencing for Detecting Recurrent Gene Fusions in Hematologic Malignancies
Publication date: Available online 19 October 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Borahm Kim, Hyeonah Lee, Saeam Shin, Seung-Tae Lee, Jong Rak ChoiABSTRACTThe application of next-generation sequencing (NGS) technology in clinical diagnostics should proceed with care. We have evaluated the clinical validity of two commercially available RNA fusion panels, the TruSight RNA fusion panel (Illumina) and FusionPlex Pan-Heme Kit (ArcherDx), to detect recurrent translocations in hematologic malignancies. Twenty-four bone marrow samples taken at the initial diagnosis of patients with acute leukemia and chroni...
Source: The Journal of Molecular Diagnostics - October 20, 2018 Category: Pathology Source Type: research

Expedited analysis and reporting of multiple mutations that modify medical management in myeloid malignancies:: It’s about (turn-around) time!
Publication date: Available online 19 October 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Michael J. Kluk, Adam Bagg (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - October 20, 2018 Category: Pathology Source Type: research

Optimized digital droplet PCR for BCR-ABL
We report here primer probe set testing ad step by step optimization of a duplex ddPCR for BCR-ABL/ABL. The optimization of ddPCR parameters increased ABL and BCR-ABL fluorescence signals by 2 and 5 fold, respectively, and enhanced the resolution between positive and negative drops. The optimized procedure generates a background false positive rate of 5% of samples and reliably detects BCR-ABL/ABL down to 1/100000 (CV
Source: The Journal of Molecular Diagnostics - October 20, 2018 Category: Pathology Source Type: research

Abstracts
Publication date: November 2018Source: The Journal of Molecular Diagnostics, Volume 20, Issue 6Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - October 19, 2018 Category: Pathology Source Type: research

Editorial Board
Publication date: November 2018Source: The Journal of Molecular Diagnostics, Volume 20, Issue 6Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - October 19, 2018 Category: Pathology Source Type: research

Table of Contents
Publication date: November 2018Source: The Journal of Molecular Diagnostics, Volume 20, Issue 6Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - October 19, 2018 Category: Pathology Source Type: research

Disclosure Statement
Publication date: November 2018Source: The Journal of Molecular Diagnostics, Volume 20, Issue 6Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - October 19, 2018 Category: Pathology Source Type: research

A Head-to-Head Analytical Comparison of Cobas 4800 HPV, PapilloCheck HPV Screening, and LMNX Genotyping Kit HPV GP for Detection of Human Papillomavirus DNA in Cervical and Cervicovaginal Swabs
In conclusion, all of the detection methods evaluated were highly sensitive and specific for hrHPV detection from both clinician-collected cervical swabs and self-sampled cervicovaginal swabs. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - October 19, 2018 Category: Pathology Source Type: research

Title Page
Publication date: November 2018Source: The Journal of Molecular Diagnostics, Volume 20, Issue 6Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - October 19, 2018 Category: Pathology Source Type: research

Author Index
Publication date: November 2018Source: The Journal of Molecular Diagnostics, Volume 20, Issue 6Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - October 19, 2018 Category: Pathology Source Type: research

Electric Field–Induced Release and Measurement Liquid Biopsy for Noninvasive Early Lung Cancer Assessment
Publication date: Available online 8 October 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Fang Wei, Charles M. Strom, Jordan Cheng, Chien-Chung Lin, Ching-Yun Hsu, Guy W. Soo Hoo, David Chia, Yong Kim, Feng Li, David Elashoff, Tristan Grognan, Michael Tu, Wei Liao, Rena Xian, Wayne W. Grody, Wu-Chou Su, David T.W. WongPreviously, we detected circulating tumor DNA that contained two EGFR mutations (p.L858R and exon19 del) in plasma of patients with late-stage non–small-cell lung carcinoma (NSCLC) using the electric field–induced release and measurement (EFIRM) platform. Our aim was to determin...
Source: The Journal of Molecular Diagnostics - October 9, 2018 Category: Pathology Source Type: research

An optimized workflow to evaluate estrogen receptor gene mutations in small amounts of cell-free DNA
Publication date: Available online 6 October 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Silvia R. Vitale, Anieta M. Sieuwerts, Nick Beije, Jaco Kraan, Lindsay Angus, Bianca Mostert, Esther A. Reijm, Ngoc M. Van, Ronald van Marion, Luc Y. Dirix, Paul Hamberg, Felix E. de Jongh, Agnes Jager, John A. Foekens, Paolo Vigneri, Stefan Sleijfer, Maurice P.H.M. Jansen, John W.M. MartensThe detection of mutated genes in cell-free DNA (cfDNA) in plasma has emerged as an important minimally-invasive way to obtain detailed information regarding tumor biology. Reliable determination of circulating tumor–derived DNA...
Source: The Journal of Molecular Diagnostics - October 6, 2018 Category: Pathology Source Type: research

The next generation in detection of leukemia-associated translocations
Publication date: Available online 27 September 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Daniel E. Sabath (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - October 5, 2018 Category: Pathology Source Type: research

Targeted next-generation sequencing facilitates genetic diagnosis and provides novel pathogenetic insights into deafness with enlarged vestibular aqueduct
Publication date: Available online 28 September 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Yin-Hung Lin, Chen-Chi Wu, Yi-Hsin Lin, Ying-Chang Lu, Chih-Shan Chen, Tien-Chen Liu, Pei-Lung Chen, Chuan-Jen HsuABSTRACTEnlarged vestibular aqueduct (EVA) is an inner ear malformation associated with sensorineural hearing impairment. The majority of EVA are associated with Pendred syndrome and non-syndromic DFNB4, two autosomal recessive disorders caused by mutations in SLC26A4. However, a significant percentage of EVA patients cannot have confirmed diagnosis by screening common SLC26A4 mutations, constituting an en...
Source: The Journal of Molecular Diagnostics - October 5, 2018 Category: Pathology Source Type: research

DETEQT: Algorithms for Adjudicating Targeted Infectious Disease Next-Generation Sequencing Panels
Publication date: Available online 28 September 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Turner A. Conrad, Chien-Chi Lo, Jeffrey W. Koehler, Amanda S. Graham, Christopher P. Stefan, Adrienne T. Hall, Christina E. Douglas, Patrick Sam Guy Chain, Timothy D. MinogueABSTRACTNext-generation sequencing (NGS) for infectious disease diagnostics is a relatively new and under-developed concept. If this technology is to become a regulatory-grade clinical diagnostic, standardization in the form of locked-down assays and firmly established underlying processes is necessary. Targeted sequencing, specifically by amplifi...
Source: The Journal of Molecular Diagnostics - October 5, 2018 Category: Pathology Source Type: research

An Innovative Multiplexed And Flexible Molecular Approach For The Differential Detection Of Arboviruses
Publication date: Available online 28 September 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Fanny Leon, Albert Meyer, Robin Reynier, Emilie Blanc, Lilian Bruyère-Ostells, Jean-Charles Brès, Yannick Simonin, Sara Salinas, Pierre Gallian, Isabelle Leparc-Goffart, Antoine Biron, Myrielle Dupont-Rouzeyrol, François Morvan, Jean-Jacques Vasseur, Vincent Foulongne, Philippe Van de Perre, Jean-François Cantaloube, Chantal Fournier-WirthAbstractNucleic acid testing during the preseroconversion viremic phase is required to differentially diagnose arboviral infections. The continuing emerge...
Source: The Journal of Molecular Diagnostics - October 5, 2018 Category: Pathology Source Type: research

A nanopore sequencing–based assay for rapid detection of gene fusions
In conclusion, we have developed a Nanopore-based sequencing assay that can decrease turnaround time for detection of fusion oncogenes and may be a valid approach for laboratories with low specimen volume and for cases in need of rapid results. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - October 5, 2018 Category: Pathology Source Type: research

A single-tube, EuroClonality-inspired, TRG clonality multiplex PCR aids management of patients with enteropathic diseases, including from formaldehyde-fixed, paraffin-embedded tissues
Publication date: Available online 28 September 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Coralie Derrieux, Amélie Trinquand, Julie Bruneau, Virginie Verkarre, Ludovic Lhermitte, Marion Alcantara, Patrick Villarese, Bertrand Meresse, David Sibon, Olivier Hermine, Nicole Brousse, Thierry Molina, Christophe Cellier, Nadine Cerf-Bensussan, Georgia Malamut, Elizabeth MacintyreAbstractCeliac disease is a chronic inflammation of the small intestine with villous atrophy that can become refractory to a gluten-free diet. Two categories of refractory celiac disease (I and II) can be distinguished by the pheno...
Source: The Journal of Molecular Diagnostics - October 5, 2018 Category: Pathology Source Type: research

Accurate and sensitive analysis of minimal residual disease in acute myeloid leukemia using deep sequencing of single nucleotide variations
In conclusion, deep sequencing enables reliable detection of low levels of residual leukemic cells. Introduction of this method in patient care will allow for highly sensitive MRD surveillance in virtually every patient with AML. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - October 5, 2018 Category: Pathology Source Type: research

insiM: in silico Mutator software for bioinformatics pipeline validation of clinical next-generation sequencing (NGS) assays
Publication date: Available online 29 September 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Sushant A. Patil, Ibro Mujacic, Lauren L. Ritterhouse, Jeremy P. Segal, Sabah KadriAbstractLack of reliable reference samples containing different mutations of interest across large sets of disease-relevant loci limits the extensive validation clinical next-generation sequencing (NGS) assays and their associated bioinformatics pipelines. Here, we have created a publicly available, highly flexible tool, in silico Mutator (insiM) to introduce point mutations, insertions, deletions, and duplications of any size into real...
Source: The Journal of Molecular Diagnostics - October 5, 2018 Category: Pathology Source Type: research

Screening for regulatory variants in 460kb encompassing the CFTR locus in cystic fibrosis patients
Publication date: Available online 5 October 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Jenny L. Kerschner, Sujana Ghosh, Alekh Paranjapye, Wilmel R. Cosme, Marie-Pierre Audrézet, Miyuki Nakakuki, Hiroshi Ishiguro, Claude Férec, Johanna Rommens, Ann HarrisABSTRACTIt is estimated that up to 5% of cystic fibrosis transmembrane conductance regulator (CFTR) pathogenic alleles are unidentified. Some of these errors may lie in non-coding regions of the locus and impact gene expression. To identify regulatory element variants in the CFTR locus, SureSelect targeted enrichment of 460kb encompassing the...
Source: The Journal of Molecular Diagnostics - October 5, 2018 Category: Pathology Source Type: research

A Head-to-Head Analytical Comparison of Cobas 4800 HPV, PapilloCheck HPV: Screening, and LMNX Genotyping Kit HPV GP for Detection of Human Papillomavirus DNA in Cervical and Cervicovaginal Swabs
In conclusion, all of the detection methods evaluated were highly sensitive and specific for hrHPV detection from both clinician-collected cervical swabs and self-sampled cervicovaginal swabs. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - September 13, 2018 Category: Pathology Source Type: research

Analytical Validation of Clinical Whole-Genome and Transcriptome Sequencing of Patient-Derived Tumors: Clinical Application of Whole-Genome Sequencing for Reporting Targetable Variants in Cancer
Publication date: Available online 21 August 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Kazimierz O. Wrzeszczynski, Vanessa Felice, Avinash Abhyankar, Lukasz Kozon, Heather Geiger, Dina Manaa, Ferrah London, Dino Robinson, Xiaolan Fang, David Lin, Michelle F. Lamendola-Essel, Depinder Khaira, Esra Dikoglu, Anne-Katrin Emde, Nicolas Robine, Minita Shah, Kanika Arora, Olca Basturk, Umesh Bhanot, Alex KentsisWe developed and validated a clinical whole-genome and transcriptome sequencing (WGTS) assay that provides a comprehensive genomic profile of a patient's tumor. The ability to fully capture the mappable ge...
Source: The Journal of Molecular Diagnostics - September 12, 2018 Category: Pathology Source Type: research

Noninvasive Molecular Monitoring in Multiple Myeloma Patients Using Cell-Free Tumor DNA: A Pilot Study
Publication date: Available online 28 August 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Giulia Biancon, Silvia Gimondi, Antonio Vendramin, Cristiana Carniti, Paolo CorradiniNovel treatments for multiple myeloma (MM) have increased rates of complete response, raising interest in more accurate methods to evaluate residual disease. Cell-free tumor DNA (cfDNA) analysis may represent a minimally invasive approach complementary to multiparameter flow cytometry (MFC) and molecular methods on bone marrow aspirates. A sequencing approach using the Ion Torrent Personal Genome Machine was applied to identify clonal IG...
Source: The Journal of Molecular Diagnostics - September 12, 2018 Category: Pathology Source Type: research

OncoKids: A Comprehensive Next-Generation Sequencing Panel for Pediatric Malignancies
We describe the validation of this panel by using a large cohort of 192 unique clinical samples that included a wide range of tumor types and alterations. Robust performance was observed for analytical sensitivity, reproducibility, and limit of detection studies. The results from this study support the use of OncoKids for routine clinical testing of a wide variety of pediatric malignancies. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - September 7, 2018 Category: Pathology Source Type: research

Clinical Significance of DNA Variants in Chronic Myeloid Neoplasms: A Report of the Association for Molecular Pathology
Publication date: Available online 20 August 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Rebecca F. McClure, Mark D. Ewalt, Jennifer Crow, Robyn L. Temple-Smolkin, Mrudula Pullambhatla, Rachel Sargent, Annette S. KimTo address the clinical relevance of small DNA variants in chronic myeloid neoplasms (CMNs), an Association for Molecular Pathology Working Group comprehensively reviewed published literature, summarized key findings that support clinical utility, and defined critical gene inclusions for high-throughput sequencing testing panels. This review highlights the biological complexity of CMNs [including...
Source: The Journal of Molecular Diagnostics - September 1, 2018 Category: Pathology Source Type: research

Describing the Reportable Range Is Important for Reliable Treatment Decisions: A Multiple Laboratory Study for Molecular Tumor Profiling Using Next-Generation Sequencing
Publication date: Available online 26 July 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Véronique Tack, Lien Spans, Ed Schuuring, Cleo Keppens, Karen Zwaenepoel, Patrick Pauwels, Jeroen Van Houdt, Elisabeth M.C. DequekerBecause interpretation of next-generation sequencing (NGS) data remains challenging, optimization of the NGS process is needed to obtain correct sequencing results. Therefore, extensive validation and continuous monitoring of the quality is essential. NGS performance was compared with traditional detection methods and technical quality of nine NGS technologies was assessed. First, nine ...
Source: The Journal of Molecular Diagnostics - August 28, 2018 Category: Pathology Source Type: research

Non-invasive molecular monitoring in multiple myeloma patients using cell-free tumor DNA: a pilot study
Publication date: Available online 28 August 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Giulia Biancon, Silvia Gimondi, Antonio Vendramin, Cristiana Carniti, Paolo CorradiniAbstractNovel treatments for multiple myeloma (MM) have increased rates of complete response raising interest in more accurate methods to evaluate residual disease. Cell-free tumor DNA (cfDNA) analysis may represent a minimally invasive approach complementary to multiparameter flow cytometry (MFC) and molecular methods on bone marrow aspirates. A sequencing approach using the Ion Torrent Personal Genome Machine was applied to identify cl...
Source: The Journal of Molecular Diagnostics - August 28, 2018 Category: Pathology Source Type: research

A head-to-head analytical comparison of cobas® 4800 HPV, PapilloCheck® HPV – Screening, and LMNX Genotyping Kit HPV GP for detection of human papillomavirus DNA in cervical and cervicovaginal swabs,
In conclusion, all the detection methods evaluated were highly sensitive and specific for hrHPV detection from both clinician-collected cervical swabs and self-sampled cervicovaginal swabs. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - August 28, 2018 Category: Pathology Source Type: research

Effects of collection and processing procedures on plasma circulating cell-free DNA from cancer patients
This study investigates the effects of the i) delay in processing, ii) storage temperatures, iii) different blood collection tubes, iv) centrifugation protocols, and v) sample shipment on cfDNA levels. Peripheral blood (n=231) from cancer patients (n=62) were collected into K3EDTA or Cell-free DNA BCT® (BCT) tubes and analyzed by digital PCR, targeted amplicon, or shallow whole-genome (sWGS) sequencing. To assess pre-analytic effects, plasma was processed under different conditions after 0h, 6h, 24h, 48h, 96h, and 1 week at room temperature or 4 °C, or using different centrifugation protocols. Digital PCR showed th...
Source: The Journal of Molecular Diagnostics - August 28, 2018 Category: Pathology Source Type: research

Diagnostic targeted sequencing panel for hepatocellular carcinoma genomic screening
In conclusion, we established a cost-effective assay for the detection of genomic alterations in HCC. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - August 23, 2018 Category: Pathology Source Type: research

Analytical Validation of Clinical Whole-Genome and Transcriptome Sequencing of Patient Derived Tumors Clinical Application of Whole-Genome Sequencing for Reporting Targetable Variants in Cancer
Publication date: Available online 21 August 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Kazimierz O. Wrzeszczynski, Vanessa Felice, Avinash Abhyankar, Lukasz Kozon, Heather Geiger, Dina Manaa, Ferrah London, Dino Robinson, Xiaolan Fang, David Lin, Michelle F. Lamendola-Essel, Depinder Khaira, Esra Dikoglu, Anne-Katrin Emde, Nicolas Robine, Minita Shah, Kanika Arora, Olca Basturk, Umesh Bhanot, Alex KentsisWe have developed and validated a clinical whole-genome and transcriptome sequencing (WGTS) assay which provides a comprehensive genomic profile of a patient’s tumor. The ability to fully capture the...
Source: The Journal of Molecular Diagnostics - August 21, 2018 Category: Pathology Source Type: research

Validation of a Long-Read PCR Assay for Sensitive Detection and Sizing of C9orf72 Hexanucleotide Repeat Expansions
Publication date: Available online 20 August 2018Source: The Journal of Molecular DiagnosticsAuthor(s): EunRan Suh, Kaitlyn Grando, Vivianna M. Van DeerlinA hexanucleotide GGGGCC repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). Accurate determination and quantitation of the repeat length is critical in both clinical and research settings. However, due to the complexity of the C9orf72 expansion with high GC content, large size of repeats, and high rate of insertion/deletions (indels) and sequence variations in the flanking regions, mol...
Source: The Journal of Molecular Diagnostics - August 21, 2018 Category: Pathology Source Type: research

Clinical Significance of DNA Variants in Chronic Myeloid Neoplasms (CMNs): A Report of the Association for Molecular Pathology
Publication date: Available online 20 August 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Rebecca F. McClure, Mark D. Ewalt, Jennifer Crow, Robyn L. Temple-Smolkin, Mrudula Pullambhatla, Rachel Sargent, Annette S. KimAbstractTo address the clinical relevance of small DNA variants in chronic myeloid neoplasms (CMNs), an Association for Molecular Pathology (AMP) Working Group comprehensively reviewed published literature, summarized key findings that support clinical utility, and defined critical gene inclusions for high-throughput sequencing testing panels. This review highlights the biological complexity of C...
Source: The Journal of Molecular Diagnostics - August 21, 2018 Category: Pathology Source Type: research

OncoKidsSM: A Comprehensive Next-Generation Sequencing Panel for Pediatric Malignancies
We describe the validation of this panel using a large cohort of 192 unique clinical samples that included a wide range of tumor types and alterations. Robust performance was observed for analytical sensitivity, reproducibility, and limit of detection studies. The results from this study support the use of OncoKidsSM for routine clinical testing of a wide variety of pediatric malignancies. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - August 21, 2018 Category: Pathology Source Type: research

Editorial Board
Publication date: September 2018Source: The Journal of Molecular Diagnostics, Volume 20, Issue 5Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - August 21, 2018 Category: Pathology Source Type: research

Table of Contents
Publication date: September 2018Source: The Journal of Molecular Diagnostics, Volume 20, Issue 5Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - August 21, 2018 Category: Pathology Source Type: research