FOXL2 402C > G Mutation Can Be Identified in the Circulating Tumor DNA of Patients with Adult Granulosa Cell Tumors
Adult granulosa cell tumors (AGCTs) of the ovary are molecularly characterized by the pathognomonic FOXL2 402C>G (C134W) mutation. To improve diagnostics and follow-up, we developed a specific digital droplet PCR (ddPCR) assay to detect the FOXL2 mutation in the circulating tumor DNA (ctDNA) of AGCT patients. Optimization of the ddPCR assay was performed using a TaqMan primer/probe with the RainDance RainDrop digital PCR system. The ddPCR assay was performed on circulating cell-free DNA extracted from 120 serial plasma samples collected prospectively from 35 AGCT patients. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 31, 2016 Category: Pathology Authors: Anniina F ärkkilä, Melissa K. McConechy, Winnie Yang, Aline Talhouk, Ying Ng, Amy Lum, Ryan D. Morin, Kevin Bushell, Annika Riska, Jessica N. McAlpine, C. Blake Gilks, Leila Unkila-Kallio, Mikko Anttonen, David G. Huntsman Tags: Regular Article Source Type: research

Comparison of Next-Generation Sequencing Panels and Platforms for Detection and Verification of Somatic Tumor Variants for Clinical Diagnostics
Use of next-generation sequencing to detect somatic variants in DNA extracted from formalin-fixed, paraffin-embedded tumor tissues poses a challenge for clinical molecular diagnostic laboratories because of variable DNA quality and quantity, and the potential to detect low allele frequency somatic variants difficult to verify by non –next-generation sequencing methods. We evaluated somatic variant detection performance of the MiSeq and Ion Proton benchtop sequencers using two commercially available panels, the TruSeq Amplicon Cancer Panel and the AmpliSeq Cancer Hotspot Panel Version 2. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 19, 2016 Category: Pathology Authors: Maksym Misyura, Tong Zhang, Mahadeo A. Sukhai, Mariam Thomas, Swati Garg, Suzanne Kamel-Reid, Tracy L. Stockley Tags: Regular article Source Type: research

Emerging and Future Applications of Matrix-Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry in the Clinical Microbiology Laboratory
The performance of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MS) for routine bacterial and yeast identification as well as direct-from-blood culture bottle identification has been thoroughly evaluated in the peer-reviewed literature. Microbiologists are now moving beyond these methods to apply MS to other areas of the diagnostic process. This review discusses the emergence of advanced matrix-assisted laser desorption ionization time-of-flight MS applications, including the identification of filamentous fungi and mycobacteria and the current and future state of  antimicrobial resista...
Source: Journal of Molecular Diagnostics - October 19, 2016 Category: Pathology Authors: Christopher D. Doern, Susan M. Butler-Wu Tags: Special article Source Type: research

Editorial Board
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 19, 2016 Category: Pathology Source Type: research

Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 19, 2016 Category: Pathology Source Type: research

Title Page
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 19, 2016 Category: Pathology Source Type: research

Disclosures Statement
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 19, 2016 Category: Pathology Source Type: research

Abstracts
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 19, 2016 Category: Pathology Source Type: research

Author Index
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 19, 2016 Category: Pathology Source Type: research

Validation of a Clinical-Grade Assay to Measure Donor-Derived Cell-Free DNA in Solid Organ Transplant Recipients
The use of circulating cell-free DNA (cfDNA) as a biomarker in transplant recipients offers advantages over invasive tissue biopsy as a quantitative measure for detection of transplant rejection and immunosuppression optimization. However, the fraction of donor-derived cfDNA (dd-cfDNA) in transplant recipient plasma is low and challenging to quantify. Previously reported methods to measure dd-cfDNA require donor and recipient genotyping, which is impractical in clinical settings and adds cost. We developed a targeted next-generation sequencing assay that uses 266 single-nucleotide polymorphisms to accurately quantify dd-cf...
Source: Journal of Molecular Diagnostics - October 7, 2016 Category: Pathology Authors: Marica Grskovic, David J. Hiller, Lane A. Eubank, John J. Sninsky, Cindy Christopherson, John P. Collins, Kathryn Thompson, Mindy Song, Yue S. Wang, David Ross, Mitchell J. Nelles, James P. Yee, Judith C. Wilber, Maria G. Crespo-Leiro, Susan L. Scott, Rob Tags: Regular Article Source Type: research

Sanger Confirmation Is Required to Achieve Optimal Sensitivity and Specificity in Next-Generation Sequencing Panel Testing
Next-generation sequencing (NGS) has rapidly replaced Sanger sequencing as the method of choice for diagnostic gene-panel testing. For hereditary-cancer testing, the technical sensitivity and specificity of the assay are paramount as clinicians use results to make important clinical management and treatment decisions. There is significant debate within the diagnostics community regarding the necessity of confirming NGS variant calls by Sanger sequencing, considering that numerous laboratories report having 100% specificity from the NGS data alone. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 6, 2016 Category: Pathology Authors: Wenbo Mu, Hsiao-Mei Lu, Jefferey Chen, Shuwei Li, Aaron M. Elliott Tags: Regular Article Source Type: research

Next-Generation Sequencing in Cancer Diagnostics
This commentary highlights the article by Misyura et  al that underscores the use of next-generation sequencing platforms for detection and verification of somatic variants. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - September 21, 2016 Category: Pathology Authors: Christopher L. Corless Tags: Commentary Source Type: research

Correction
In the article entitled, “Performance Characteristics and Validation of Next-Generation Sequencing for Human Leucocyte Antigen Typing” (Volume 18, pages 668–675 of the September 2016 issue of The Journal of Molecular Diagnostics; http://dx.doi.org/10.1016/j.jmoldx.2016.03.009), there is a spelling error in the title a nd the footnotes of Table 1 and Table 3. The correct expansion of HLA is human leukocyte antigen, and the affected locations are being updated to reflect the correct spelling of leukocyte. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - September 19, 2016 Category: Pathology Tags: Correction Source Type: research

Correction
In the article entitled “Recent Advances on the Molecular Pathology of Glial Neoplasms in Children and Adults” (Volume 18, pages 620–634 of the September 2016 issue of The Journal of Molecular Diagnostics; http://dx.doi.org/10.1016/j.jmoldx.2016.05.005), the promoter mutations listed on page 628 were incorrectly labe led as proteins rather than nucleotides. The correct sentence should read: “Testing for TERT promoter mutations is relatively straightforward because they also occur at specific hotspots (C228T or C250T).” (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - September 19, 2016 Category: Pathology Tags: Correction Source Type: research

Correction
In the article entitled “Diagnostic Detection of Allelic Losses and Imbalances by Next-Generation Sequencing” (Volume 18, pages 775–786 of the September 2016 issue of The Journal of Molecular Diagnostics; http://dx.doi.org/10.1016/j.jmoldx.2016.06.002), the authors have contacted the editorial office regarding incorr ect citation numbering. On page 784, reference 23 should be cited at the end of the following sentence rather than reference 22: “As an example, we recently showed that molecular classification of gliomas better defines clinically relevant subgroups than histologic grading by combining ...
Source: Journal of Molecular Diagnostics - September 19, 2016 Category: Pathology Tags: Correction Source Type: research

Temporary Removal: Corrections
Available Online September 19, 2016The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated.The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - September 19, 2016 Category: Pathology Source Type: research

Corrections
In the article entitled, “Performance Characteristics and Validation of Next-Generation Sequencing for Human Leucocyte Antigen Typing” (Volume 18, pages 668–675 of the September 2016 issue of The Journal of Molecular Diagnostics; http://dx.doi.org/10.1016/j.jmoldx.2016.03.009), there is a spelling error in the title a nd the footnotes of Table 1 and Table 3. The correct expansion of HLA is human leukocyte antigen, and the affected locations are being updated to reflect the correct spelling of leukocyte. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - September 19, 2016 Category: Pathology Tags: Corrections Source Type: research

Corrections
In the article entitled “Recent Advances on the Molecular Pathology of Glial Neoplasms in Children and Adults” (Volume 18, pages 620–634 of the September 2016 issue of The Journal of Molecular Diagnostics; http://dx.doi.org/10.1016/j.jmoldx.2016.05.005), the promoter mutations listed on page 628 were incorrectly labe led as proteins rather than nucleotides. The correct sentence should read: “Testing for TERT promoter mutations is relatively straightforward because they also occur at specific hotspots (C228T or C250T).” (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - September 19, 2016 Category: Pathology Tags: Corrections Source Type: research

Corrections
In the article entitled “Diagnostic Detection of Allelic Losses and Imbalances by Next-Generation Sequencing” (Volume 18, pages 775–786 of the September 2016 issue of The Journal of Molecular Diagnostics; http://dx.doi.org/10.1016/j.jmoldx.2016.06.002), the authors have contacted the editorial office regarding incorr ect citation numbering. On page 784, reference 23 should be cited at the end of the following sentence rather than reference 22: “As an example, we recently showed that molecular classification of gliomas better defines clinically relevant subgroups than histologic grading by combining ...
Source: Journal of Molecular Diagnostics - September 19, 2016 Category: Pathology Tags: Corrections Source Type: research

Clinical Performance Evaluation of Molecular Diagnostic Tests
Molecular diagnostic tests with application to clinical diagnostics involve studies in infectious diseases, inherited diseases, oncology, predisposition to disease, or the description of polymorphisms linked to disease states. General considerations in the design of evaluation of diagnostic test trials and statistical principles for reporting the results are discussed. A brief overview of the general statistical considerations related to the intent of use, test development versus validation, different types of biases, and issues with missing data are provided. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - September 15, 2016 Category: Pathology Authors: Bipasa Biswas Tags: Review Source Type: research

Multiplexed Reference Materials as Controls for Diagnostic Next-Generation Sequencing
Diagnostic next-generation sequencing (NGS)-based gene panels are increasingly used for prevalent disorders with genetic and clinical heterogeneity. Clinical development, validation, and quality management of these panels ideally includes reference samples containing prevalent pathogenic variants; however, clinical domain expertise to select appropriate variants may not be present, samples are often not publicly available, and their inclusion is associated with added cost. Expert-designed, multiplexed controls can remedy some of these challenges. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - September 15, 2016 Category: Pathology Authors: Emily M. Kudalkar, Naif A.M. Almontarishi, Catherine Huang, Bharathi Anekella, Mark Bowser, Elizabeth Hynes, Russell Garlick, Birgit H. Funke Tags: Regular Article Source Type: research

The Clinical Implications of Inconsistently Methylated Results from Glioblastoma MGMT Testing by Replicate Methylation-Specific PCR
The methylation status of the promoter of the O6-methylguanine DNA methyltransferase gene (MGMT) is an established prognostic and predictive biomarker of glioblastoma (GBM). At the Center for Advanced Molecular Diagnostics, MGMT testing is performed by methylation-specific PCR with multiple replicates, leading to three types of reportable results: methylated, unmethylated, and inconsistently methylated. An inconsistently methylated result is reported when a methylated peak is seen in some but not all of the PCR replicates from a single DNA sample. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - September 14, 2016 Category: Pathology Authors: Daniel Xia, David A. Reardon, Jacqueline L. Bruce, Neal I. Lindeman Tags: Regular Article Source Type: research

Diagnosis of Primary Ciliary Dyskinesia by a Targeted Next-Generation Sequencing Panel
In this study, we clinically and molecularly characterized a cohort of 51 Italian patients with clinical signs of PCD. A custom next-generation sequencing panel that enables the affordable and simultaneous screening of 24 PCD genes was developed for genetic analysis. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - September 13, 2016 Category: Pathology Authors: Francesca Boaretto, Deborah Snijders, Cecilia Salvoro, Ambra Spalletta, Maria Luisa Mostacciuolo, Mirella Collura, Salvatore Cazzato, Donatella Girosi, Michela Silvestri, Giovanni Arturo Rossi, Angelo Barbato, Giovanni Vazza Tags: Regular Article Source Type: research

Reliable Next-Generation Sequencing of Formalin-Fixed, Paraffin-Embedded Tissue Using Single Molecule Tags
Sequencing of tumor DNA to detect genetic aberrations is getting increasingly important, not only to refine cancer diagnoses but also to predict response to targeted treatments. Next-generation sequencing is widely adopted in diagnostics for the analyses of DNA extracted from routinely processed formalin-fixed, paraffin-embedded tissue, fine-needle aspirates, or cytologic smears. PCR-based enrichment strategies are usually required to obtain sufficient read depth for reliable detection of genetic aberrations. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - September 13, 2016 Category: Pathology Authors: Astrid Eijkelenboom, Eveline Kamping, Annemiek Kastner-van Raaij, Sandra Hendriks-Cornelissen, Kornelia Neveling, Roland Kuiper, Alexander Hoischen, Marcel Nelen, Marjolijn Ligtenberg, Bastiaan Tops Tags: Regular Article Source Type: research

Clinical Application of Picodroplet Digital PCR Technology for Rapid Detection of EGFR T790M in Next-Generation Sequencing Libraries and DNA from Limited Tumor Samples
Although next-generation sequencing (NGS) is a robust technology for comprehensive assessment of EGFR mutant lung adenocarcinomas (LADs) with acquired resistance to tyrosine kinase inhibitors, it may not provide sufficiently rapid and sensitive detection of the EGFR T790M mutation, the most clinically relevant resistance biomarker. Here, we describe a digital PCR (dPCR) assay for rapid T790M detection on aliquots of NGS libraries prepared for comprehensive profiling, fully maximizing broad genomic analysis on limited samples. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - September 12, 2016 Category: Pathology Authors: Laetitia Borsu, Julie Intrieri, Linta Thampi, Helena Yu, Gregory Riely, Khedoudja Nafa, Raghu Chandramohan, Marc Ladanyi, Maria E. Arcila Tags: Regular Article Source Type: research

Improved Diagnosis of Inherited Retinal Dystrophies by High-Fidelity PCR of ORF15 followed by Next-Generation Sequencing
Retinitis pigmentosa (RP) is the most common form of retinal dystrophy. The disease is characterized by the progressive degeneration of photoreceptors, ultimately leading to blindness. The exon ORF15 of RP  GTPase regulator (RPGR) is a mutation hot spot for X-linked RP and one form of cone dystrophy. However, accurate molecular testing of ORF15 is challenging because of a large segment of highly repetitive purine-rich sequence in this exon. ORF15 performs poorly in next-generation sequencing–base d panels or whole exome sequencing analysis, whereas Sanger sequencing of ORF15 requires special reagents a...
Source: Journal of Molecular Diagnostics - September 12, 2016 Category: Pathology Authors: Jianli Li, Jia Tang, Yanming Feng, Mingchu Xu, Rui Chen, Xuan Zou, Ruifang Sui, Emmanuel Y. Chang, Richard A. Lewis, Victor W. Zhang, Jing Wang, Lee-Jun C. Wong Tags: Technical Advance Source Type: research

Improving Accuracy of Urinary miRNA Quantification in Heparinized Patients Using Heparinase I Digestion
miRNAs have emerged as promising biomarkers because of their association with cell stress and diseases and their easy detection and stability in many body fluids. Because of the sensitivity, the method of choice to detect miRNAs is quantitative RT-PCR (RT-qPCR). Therapeutics, in particular circulating anticoagulants, are notorious for their inhibitory effect on RT-qPCR –based measurements. The effect of heparin contamination on inhibition of RT-qPCR from miRNAs isolated from urine has, however, never been investigated. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - September 3, 2016 Category: Pathology Authors: Henk P. Roest, Cornelia J. Verhoeven, Jubi E. de Haan, Jeroen de Jonge, Jan N.M. IJzermans, Luc J.W. van der Laan Tags: Technical Advance Source Type: research

CNV-RF Is a Random Forest –Based Copy Number Variation Detection Method Using Next-Generation Sequencing
Simultaneous detection of small copy number variations (CNVs) ( (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - September 2, 2016 Category: Pathology Authors: Getiria Onsongo, Linda B. Baughn, Matthew Bower, Christine Henzler, Matthew Schomaker, Kevin A.T. Silverstein, Bharat Thyagarajan Tags: Regular Article Source Type: research

Clinical Validation of Fragile X Syndrome Screening by DNA Methylation Array
Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. It is most frequently caused by an abnormal expansion of the CGG trinucleotide repeat (>200 repeats) located in the promoter of the fragile X mental retardation gene (FMR1), resulting in promoter DNA hypermethylation and gene silencing. Current clinical tests for FXS are technically challenging and labor intensive, and may involve use of hazardous chemicals or radioisotopes. We clinically validated the Illumina Infinium HumanMethylation450 DNA methylation array for FXS screening. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - August 29, 2016 Category: Pathology Authors: Laila C. Schenkel, Charles Schwartz, Cindy Skinner, David Rodenhiser, Peter Ainsworth, Guillaume Pare, Bekim Sadikovic Tags: Technical Advance Source Type: research

Clinical Validity and Utility
This commentary highlights the article by Joseph et  al that provides guidelines for ascribing patient-centric clinical utility and validity parameters. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - August 20, 2016 Category: Pathology Authors: Daniel H. Farkas Tags: Commentary Source Type: research

Editorial Board
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - August 20, 2016 Category: Pathology Source Type: research

Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - August 20, 2016 Category: Pathology Source Type: research

Correction
In the article entitled, “External Quality Assessment for Detection of Fetal Trisomy 21, 18, and 13 by Massively Parallel Sequencing in Clinical Laboratories” (Volume 18, pages 244–252 of the March 2016 issue of The Journal of Molecular Diagnostics; http://dx.doi.org/10.1016/j.jmoldx.2015.10.003), the departments and institutions of the authors listed are incorrect. The correct affiliation list is as follows: (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - August 20, 2016 Category: Pathology Tags: Correction Source Type: research

The Spectrum of Clinical Utilities in Molecular Pathology Testing Procedures for Inherited Conditions and Cancer
Clinical utility describes the benefits of each laboratory test for that patient. Many stakeholders have adopted narrow definitions for the clinical utility of molecular testing as applied to targeted pharmacotherapy in oncology, regardless of the population tested or the purpose of the testing. This definition does not address all of the important applications of molecular diagnostic testing. Definitions consistent with a patient-centered approach emphasize and recognize that a clinical test result's utility depends on the context in which it is used and are particularly relevant to molecular diagnostic testing because of...
Source: Journal of Molecular Diagnostics - August 16, 2016 Category: Pathology Authors: Loren Joseph, Milena Cankovic, Samuel Caughron, Pranil Chandra, Rajyasree Emmadi, Jill Hagenkord, Stephanie Hallam, Kay E. Jewell, Roger D. Klein, Victoria M. Pratt, Paul G. Rothberg, Robyn L. Temple-Smolkin, Elaine Lyon Tags: Special Article Source Type: research

A Set of Assays for the Comprehensive Analysis of FMR1 Alleles in the Fragile X –Related Disorders
The diagnosis and study of the fragile X –related disorders is complicated by the difficulty of amplifying the long CGG/CCG-repeat tracts that are responsible for disease pathology, the potential presence of AGG interruptions within the repeat tract that can ameliorate expansion risk, the occurrence of variable DNA methylation that modul ates disease severity, and the high frequency of mosaicism for both repeat number and methylation status. These factors complicate patient risk assessment. In addition, the variability in these parameters that is seen when patient cells are grown in culture requires their frequent mo...
Source: Journal of Molecular Diagnostics - August 12, 2016 Category: Pathology Authors: Bruce E. Hayward, Yifan Zhou, Daman Kumari, Karen Usdin Tags: Regular Article Source Type: research

Health Care Infrastructure for Financially Sustainable Clinical Genomics
Next-generation sequencing has evolved technically and economically into the method of choice for interrogating the genome in cancer and inherited disorders. The introduction of procedural code sets for whole-exome and genome sequencing is a milestone toward financially sustainable clinical implementation; however, achieving reimbursement is currently a major challenge. As part of a prospective quality-improvement initiative to implement the new code sets (January 2015), we adopted agile, a development methodology originally devised in software development. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 25, 2016 Category: Pathology Authors: Jochen K. Lennerz, Heather M. McLaughlin, Jason M. Baron, David Rasmussen, Meini Sumbada Shin, Nancy Berners-Lee, Julie Miller Batten, Kathryn J. Swoboda, Manish K. Gala, Harland S. Winter, Jeremy D. Schmahmann, David A. Sweetser, Marianne Boswell, Maciej Source Type: research

Diagnostic Detection of Allelic Losses and Imbalances by Next-Generation Sequencing
Cancer cells are genomic unstable and accumulate tumor type –specific molecular aberrations, which may represent hallmarks for predicting prognosis and targets for therapy. Co-deletion of chromosomes 1p and 19q marks gliomas with an oligodendroglioma component and predicts a better prognosis and response to chemotherapy. In the current study, we present a novel method to detect chromosome 1p/19q co-deletion or loss of heterozygosity (LOH) in a diagnostic setting, based on single-nucleotide polymorphism (SNP) analysis and next-generation sequencing (NGS) on an Ion Torrent platform. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 23, 2016 Category: Pathology Authors: Hendrikus J. Dubbink, Peggy N. Atmodimedjo, Ronald van Marion, Peter H.J. Riegman, Johan M. Kros, Martin J. van den Bent, Winand N.M. Dinjens Tags: Regular Article Source Type: research

Certified DNA Reference Materials to Compare HER2 Gene Amplification Measurements Using Next-Generation Sequencing Methods
The National Institute of Standards and Technology (NIST) Standard Reference Materials 2373 is a set of genomic DNA samples prepared from five breast cancer cell lines with certified values for the ratio of the HER2 gene copy number to the copy numbers of reference genes determined by real-time quantitative and digital PCR. Targeted-amplicon, whole-exome, and whole-genome sequencing measurements were used with the reference material to compare the performance of both the laboratory steps and the bioinformatic approaches of the different methods using a range of amplification ratios. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 22, 2016 Category: Pathology Authors: Chih-Jian Lih, Han Si, Biswajit Das, Robin D. Harrington, Kneshay N. Harper, David J. Sims, Paul M. McGregor, Corinne E. Camalier, Andrew Y. Kayserian, P. Mickey Williams, Hua-Jun He, Jamie Almeida, Steve Lund, Steve Choquette, Kenneth D. Cole Tags: Regular Article Source Type: research

Rapid Molecular Profiling of Myeloproliferative Neoplasms Using Targeted Exon Resequencing of 86 Genes Involved in JAK-STAT Signaling and Epigenetic Regulation
Myeloproliferative neoplasms (MPNs) are a heterogeneous group of blood disorders characterized by excess production of mature blood cells and an increased risk of late transformation to acute myeloid leukemia or primary myelofibrosis. Approximately 15% of MPN cases do not carry mutations in JAK2, CALR, or MPL and are thus often referred to as triple-negative cases. These are caused by a diverse set of rare mutations in cytokine receptors, Janus kinase-STAT signaling pathway components, or epigenetic modifiers. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - July 19, 2016 Category: Pathology Authors: Graham W. Magor, Michael R. Tallack, Nathan M. Klose, Debra Taylor, Darren Korbie, Peter Mollee, Matt Trau, Andrew C. Perkins Tags: Regular Article Source Type: research

Recent Advances on the Molecular Pathology of Glial Neoplasms in Children and Adults
Gliomas represent the most common primary intraparenchymal tumors of the central nervous system in adults and children and are a genetic and phenotypic heterogeneous group. Large multi-institutional studies and The Cancer Genome Atlas have provided firm insights into the basic genetic drivers in gliomas. The main molecular biomarkers routinely applied to evaluate diffuse gliomas include MGMT promoter methylation, EGFR alterations (eg, EGFRvIII), IDH1 or IDH2 mutations, and 1p19q co-deletion. Many of these markers have become standard of care for molecular testing and prerequisites for clinical trial enrollment. (Source: Jo...
Source: Journal of Molecular Diagnostics - July 18, 2016 Category: Pathology Authors: Fausto J. Rodriguez, M. Adelita Vizcaino, Ming-Tseh Lin Tags: Review Source Type: research

Implementation of a Reliable Next-Generation Sequencing Strategy for Molecular Diagnosis of Dystrophinopathies
Diagnosis of dystrophinopathies needs to combine several techniques for detecting copy number variations (CNVs; two-thirds of mutations) and single nucleotide variations (SNVs). We participated in the design of an amplicon-based PCR kit (Multiplicom) for sequencing with a GS-Junior instrument (Roche) and later with a MiSeq instrument (Illumina). We compared two different software programs, MiSeq Reporter (Illumina) and SeqNext (JSI Medical Systems) for data analyses. Testing of six patient DNA samples carrying 72 SNVs in the DMD gene showed an experimental sensitivity of 91.7% with MiSeq Reporter, 98.6% with SeqNext, and&g...
Source: Journal of Molecular Diagnostics - July 14, 2016 Category: Pathology Authors: Melissa Alame, Delphine Lacourt, Reda Zenagui, D éborah Mechin, Fabienne Danton, Michel Koenig, Mireille Claustres, Mireille Cossée Tags: Regular Article Source Type: research

Mutation Spectrum of the Survival of Motor Neuron 1 and Functional Analysis of Variants in Chinese Spinal Muscular Atrophy
Proximal spinal muscular atrophy (SMA) is a common fatal autosomal recessive disorder caused by deletion or mutation of the survival of motor neuron 1 (SMN1). Here, we studied SMA molecular pathology in 653 Chinese patients and found approximately 88.2% with homozygous SMN1 exon 7 deletion and 6.3% with heterozygous exon 7 loss using multiplex ligation-dependent probe amplification. SMN1 variants were detected in 34 patients with heterozygous SMN1 loss by clone sequencing. In 27 of them, 15 variants were identified: five were unreported novel variants [c.-7_9del(p.0), p.Tyr109Cys, p.Ile249Tyrfs*16, p.Tyr272Trpfs*35, and c....
Source: Journal of Molecular Diagnostics - July 14, 2016 Category: Pathology Authors: Yu-jin Qu, Jin-li Bai, Yan-yan Cao, Hong Wang, Yu-wei Jin, Juan Du, Xiu-shan Ge, Wen-hui Zhang, Yan Li, Sheng-xi He, Fang Song Tags: Regular Article Source Type: research

Implementation of a Reliable Next-Generation Sequencing Strategy for Molecular Diagnosis of Dystrophinopathies
Diagnosis of dystrophinopathies needs to combine several techniques for detecting copy number variations (CNVs; two-thirds of mutations) and single nucleotide variations (SNVs). We participated in the design of an amplicon-based PCR kit (Multiplicom) for sequencing with a GS-Junior instrument (Roche) and later with a MiSeq instrument (Illumina). We compared two different software programs, MiSeq Reporter (Illumina) and SeqNext (JSI Medical Systems) for data analyses. Testing of six patient DNA samples carrying 72 SNVs in the DMD gene showed an experimental sensitivity of 91.8% with MiSeq Reporter, 98.6% with SeqNext, and&g...
Source: Journal of Molecular Diagnostics - July 14, 2016 Category: Pathology Authors: Melissa Alame, Delphine Lacourt, Reda Zenagui, Déborah Mechin, Fabienne Danton, Michel Koenig, Mireille Claustres, Mireille Cossée Tags: Regular Article Source Type: research