Germline mutation in 1,338 BRCA-negative Chinese hereditary breast and/or ovarian cancer patients: clinical testing with a multigene test panel
Publication date: Available online 15 February 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Ava Kwong, Vivian Yvonne Shin, Jiawei Chen, Isabella Wai-Yin Cheuk, Cecilia YS. Ho, Chun Hang Au, Karen K.L. Chan, Hextan Y.S. Ngan, Tsun Leung Chan, James M. Ford, Edmond SK. MaABSTRACTDifferences in the mutation spectrum across ethnicities suggest that it is important to identify genes in addition to common high penetrant genes to estimate the associated breast cancer risk in Chinese. 1,338 high-risk breast cancer patients who tested negative for germline BRCA1, BRCA2, TP53 and PTEN mutations between 2007-2017 were s...
Source: The Journal of Molecular Diagnostics - February 15, 2020 Category: Pathology Source Type: research

ViroPanel: Hybrid capture and massively parallel sequencing for simultaneous detection and profiling of oncogenic virus infection and tumor genome
We present a hybrid-capture and massively parallel sequencing (MPS) approach to detect viral infection that is integrated with targeted genomic analysis to provide a more complete tumor profile from a single sample. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - February 15, 2020 Category: Pathology Source Type: research

Ultrasensitive detection of NOTCH1 delCT mutations in chronic lymphocytic leukemia by ddPCR reveals high frequency of subclonal mutations and predicts clinical outcome in cases with trisomy 12
Publication date: Available online 6 February 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Catherine Hoofd, Steven J. Huang, Samuel Gusscott, Sonya Lam, Rachel Wong, Alexa Johnston, Susana Ben-Neriah, Christian Steidl, David W. Scott, Helene Bruyere, Tanya L. Gillan, Cynthia L. Toze, Alina S. Gerrie, Andrew P. WengAbstractNOTCH1 is recurrently mutated in chronic lymphocytic leukemia (CLL), most commonly as a two base-pair frameshift deletion (c.7541_7542delCT). This mutated allele encodes a truncated form of the receptor (P2514fs*4) lacking the C-terminal PEST degradation domain, and results in increased NOTC...
Source: The Journal of Molecular Diagnostics - February 8, 2020 Category: Pathology Source Type: research

Next-generation sequencing-based diagnosis of unexplained inherited hemolytic anemias reveals wide genetic and phenotypic heterogeneity
Publication date: Available online 6 February 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Manu Jamwal, Anu Aggarwal, Arindam Palodhi, Prashant Sharma, Deepak Bansal, Amita Trehan, Pankaj Malhotra, Arindam Maitra, Reena DasAbstractDetermination of the cause of inherited hemolysis is based on clinical and step-wise conventional laboratory tests. Patients with obscure etiology require genetic diagnosis which is time-consuming, expensive and laborious, mainly because of numerous causal genes. We enrolled 43 patients with clinical and laboratory evidence of unexplained hemolytic anemia. Initially, 13 patients wer...
Source: The Journal of Molecular Diagnostics - February 8, 2020 Category: Pathology Source Type: research

Assessing the diagnostic yield of targeted next-generation sequencing for melanoma and gastrointestinal tumors
In this study, we compared clinical diagnostic yield of TruSight Tumor 26 Sequencing Panel (TST26) in melanoma, colorectal (CRC) and gastro-intestinal stromal (GIST) tumors to non-NGS assays. 1041 formalin-fixed, paraffin embedded (FFPE) tumors, of melanoma, CRC and GIST were profiled. NGS results were compared to non-NGS single-gene or single-variant assays with respect to variant output and diagnostic yield. 79% melanoma and 94% CRC tumors were variant-positive by panel testing. TST26 panel improved BRAF variant detection in melanoma as compared to single-variant BRAF V600E/K routine tests by 24% and also detected varian...
Source: The Journal of Molecular Diagnostics - February 8, 2020 Category: Pathology Source Type: research

Feasibility of combined detection of gene mutations and fusion transcripts in bone marrow trephines from leukemic neoplasms
Publication date: Available online 7 February 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Stephan Bartels, Britta Hasemeier, Julia Vogtmann, Elisa Schipper, Guntram Büsche, Jerome Schlue, Hans Kreipe, Ulrich LehmannAbstractChromosomal translocations resulting in fusion genes represent important oncogenic drivers and potential therapeutic targets in rare leukemia subtypes. Formalin-fixed and paraffin-embedded trephines are frequently used in hematologic diagnostic and provide relevant access to leukemic cells for further studies, e.g. phenotyping in bone marrow fibrosis. However, high-throughput molecula...
Source: The Journal of Molecular Diagnostics - February 8, 2020 Category: Pathology Source Type: research

Molecular profiling for supernatants and matched cell pellets of pleural effusions in non-small-cell lung cancer
In conclusion, pleural effusion derived cfTNA can effectively be used in clinical practice for molecular analysis by NGS, even in cases corresponding cell pellets or tumor tissues yield insufficient material. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - February 8, 2020 Category: Pathology Source Type: research

Differential diagnosis of malignant pleural mesothelioma on cytology: a gene expression panel versus BAP1 and p16 tests.
Publication date: Available online 7 February 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Rossella Bruno, Greta Alì, Anello Marcello Poma, Agnese Proietti, Roberta Libener, Narciso Mariani, Cristina Niccoli, Antonio Chella, Alessandro Ribechini, Federica Grosso, Gabriella FontaniniABSTRACTPleural effusions are among the first clinical manifestations of malignant pleural mesothelioma (MPM) and often constitute the only available material for diagnosis. Although an MPM diagnosis can be reliable on cytology, the reported sensitivity is low (30% - 75%). Particularly, it can be hard to discriminate epithel...
Source: The Journal of Molecular Diagnostics - February 8, 2020 Category: Pathology Source Type: research

Highly sensitive blocker displacement amplification and droplet digital PCR reveal very low-level parental FOXF1 somatic mosaicism in families with ACDMPV
Publication date: Available online 7 February 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Justyna A. Karolak, Qian Liu, Nina G. Xie, Lucia R. Wu, Gustavo Rocha, Susana Fernandes, Luk Ho-ming, Ivan F. Lo, David Mowat, Elizabeth K. Fiorino, Morris Edelman, Joyce Fox, Denise A. Hayes, David Witte, Ashley Parrott, Edwina Popek, Przemyslaw Szafranski, David Yu Zhang, Paweł StankiewiczABSTRACTDetection of low-level somatic mosaicism (alternate allele fraction, AAF≤ 10%) in parents of affected individuals with the apparent de novo pathogenic variants enables more accurate estimate of recurrence risk. To date, o...
Source: The Journal of Molecular Diagnostics - February 8, 2020 Category: Pathology Source Type: research

Set up and validation of a targeted NGS approach for the diagnosis of lysosomal storage disorders
In this study, we evaluated an LSD targeted sequencing panel as a tool capable to potentially reverse this 'classic' diagnostic route. The panel includes 50 LSD genes and 230 Conserved Intronic Fragments (CIF), obtained comparing the intronic sequences of 33 placental mammals.For the validation phase we analyzed 56 positive controls, 13 biochemically diagnosed and 9 undiagnosed patients. Disease-causing variants were identified in 66% of the positive control alleles and in 62% of the biochemically diagnosed patients. Three undiagnosed patients were diagnosed. Eight patients undiagnosed by the panel were analyzed by whole e...
Source: The Journal of Molecular Diagnostics - February 8, 2020 Category: Pathology Source Type: research

Optimized PCR-based enrichment improves coverage uniformity and mutation detection in mitochondrial DNA next generation sequencing
Publication date: Available online 7 February 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Yang Liu, Shanshan Guo, Chun Yin, Xu Guo, Manling Liu, Zhidong Yuan, Zheng Zhao, Yongfeng Jia, Jinliang XingABSTRACTNext generation sequencing -based methods have been commonly used to detect mutations of mitochondrial genome. PCR amplification is a highly effective way for mtDNA enrichment before sequencing. However, it has been observed that highly variable sequencing depth within PCR amplicons severely reduces the coverage uniformity and accuracy of mutation calling. Therefore, it is necessary to develop an optimized...
Source: The Journal of Molecular Diagnostics - February 8, 2020 Category: Pathology Source Type: research

Use of Spiked Normalizers to More Precisely Quantify Tumor Markers and Viral Genomes by Massive Parallel Sequencing of Plasma DNA
In conclusion, the EndoGenus system is useful for evaluating efficiency of the total test system and for precisely quantifying target molecules. This system may benefit patients being monitored for disease burden while also tracking emerging subclones. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - February 8, 2020 Category: Pathology Source Type: research

Expanding the clinical and molecular heterogeneity of nonsyndromic inherited retinal dystrophies
This study highlights the clinical utility of targeted NGS for NS-IRD cases and the importance of full ophthalmologic examination, which allow us to set up new genotype-phenotype associations and expands the knowledge of this group of disorders. To identify the cause of disease is essential for improving the patient management, the accurate genetic counseling and to take advantage of gene therapy-based treatments. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - February 8, 2020 Category: Pathology Source Type: research

Analytical Performance of an Immunoprofiling Assay Based on RNA Models
Publication date: Available online 7 February 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Ian Schillebeeckx, Jon R. Armstrong, Jason T. Forys, Jeffrey Hiken, Jon Earls, Kevin C. Flanagan, Tiange Cui, Jarret I. Glasscock, David N. Messina, Eric J. DuncavageAbstractAs immuno-oncology drugs grow more popular in the treatment of cancer, better methods are needed to quantify the tumor immune cell component to determine which patients are most likely to benefit from treatment. Methods such as flow cytometry can accurately assess the composition of infiltrating immune cells, however show limited use in FFPE specime...
Source: The Journal of Molecular Diagnostics - February 8, 2020 Category: Pathology Source Type: research

Low-Pass Whole-Genome Sequencing as a Method of Determining Copy Number Variations in Uveal Melanoma Tissue Samples
Publication date: Available online 22 January 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Aaron B. Beasley, Jacqueline Bentel, Richard J.N. Allcock, Tersia Vermeulen, Leslie Calapre, Timothy Isaacs, Melanie R. Ziman, Fred K. Chen, Elin S. GrayAnalysis of specific somatic copy number alterations (SCNAs) using multiplex ligation-dependent probe amplification (MLPA) is used routinely as a prognostic test for uveal melanoma (UM). This technique requires relatively large amounts of input DNA, unattainable from many small fine-needle aspirate biopsy specimens. Herein, we compared the use of MLPA with whole-genome ...
Source: The Journal of Molecular Diagnostics - February 5, 2020 Category: Pathology Source Type: research

Editorial Board
Publication date: February 2020Source: The Journal of Molecular Diagnostics, Volume 22, Issue 2Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - February 5, 2020 Category: Pathology Source Type: research

Table of Contents
Publication date: February 2020Source: The Journal of Molecular Diagnostics, Volume 22, Issue 2Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - February 5, 2020 Category: Pathology Source Type: research

Direct Assessment of Single-Cell DNA Using Crudely Purified Live Cells: A Proof of Concept for Noninvasive Prenatal Definitive Diagnosis
Publication date: February 2020Source: The Journal of Molecular Diagnostics, Volume 22, Issue 2Author(s): Taisuke Sato, Yuki Ito, Osamu Samura, Hiroaki Aoki, Toru Uchiyama, Aikou Okamoto, Kenichiro HataNoninvasive testing techniques are often used for fetal diagnosis of genetic abnormalities but are limited by certain characteristics, including noninformative results. Thus, novel methods of noninvasive definitive diagnosis of fetal genetic abnormalities are needed. The aim of this study was to develop a single-cell DNA analysis method with high sensitivity and specificity that enables direct extraction of genetic informati...
Source: The Journal of Molecular Diagnostics - February 5, 2020 Category: Pathology Source Type: research

Clinical Validation of a Myeloid Next-Generation Sequencing Panel for Single-Nucleotide Variants, Insertions/Deletions, and Fusion Genes
In conclusion, the OMR panel is a highly accurate and reproducible next-generation sequencing panel for the detection of common genetic alterations in myeloid neoplasms. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - February 5, 2020 Category: Pathology Source Type: research

Preanalytical Variables for the Genomic Assessment of the Cellular and Acellular Fractions of the Liquid Biopsy in a Cohort of Breast Cancer Patients
Publication date: Available online 22 January 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Stephanie N. Shishido, Lisa Welter, Mariam Rodriguez-Lee, Anand Kolatkar, Liya Xu, Carmen Ruiz, Anna S. Gerdtsson, Sara Restrepo-Vassalli, Anders Carlsson, Joe Larsen, Emily J. Greenspan, E. Shelley Hwang, Kathryn R. Waitman, Jorge Nieva, Kelly Bethel, James Hicks, Peter KuhnLiquid biopsy allows assessment of multiple analytes, providing temporal information with potential for improving understanding of cancer evolution and clinical management of patients. Although liquid biopsies are intensely investigated for predicti...
Source: The Journal of Molecular Diagnostics - February 2, 2020 Category: Pathology Source Type: research

Validation of an in Vitro Mismatch Repair Assay Used in the Functional Characterization of Mismatch Repair Variants
Publication date: Available online 25 December 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Maribel González-Acosta, Inga Hinrichsen, Anna Fernández, Conxi Lázaro, Marta Pineda, Guido Plotz, Gabriel CapelláA significant proportion of DNA-mismatch repair (MMR) variants are classified as of unknown significance, precluding diagnosis. The in vitro MMR assay is used to assess their MMR capability, likely the most important function of an MMR protein. However, the robustness of the assay, crucial for its use in the clinical setting, has been rarely evaluated. The aim of the present...
Source: The Journal of Molecular Diagnostics - January 27, 2020 Category: Pathology Source Type: research

Diagnosing Bacteremia in Real Time Using Next-Generation Sequencing–Based Technology
Publication date: Available online 21 January 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Charles W. Stratton, Yi-Wei Tang (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - January 22, 2020 Category: Pathology Source Type: research

Pre-analytical variables for the genomic assessment of the cellular and acellular fractions of the liquid biopsy in a cohort of breast cancer patients
Publication date: Available online 22 January 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Stephanie N. Shishido, Lisa Welter, Mariam Rodriguez-Lee, Anand Kolatkar, Liya Xu, Carmen Ruiz, Anna S. Gerdtsson, Sara Restrepo-Vassalli, Anders Carlsson, Joe Larsen, Emily J. Greenspan, E. Shelley Hwang, Kathryn R. Waitman, Jorge Nieva, Kelly Bethel, James Hicks, Peter KuhnAbstractThe liquid biopsy allows assessment of multiple analytes providing temporal information with potential for improving our understanding of cancer evolution and clinical management of patients. While liquid biopsies are intensely investigated ...
Source: The Journal of Molecular Diagnostics - January 22, 2020 Category: Pathology Source Type: research

Low Pass Whole Genome Sequencing as a Method of Determining Copy Number Variations in Uveal Melanoma Tissue Samples
Publication date: Available online 22 January 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Aaron B. Beasley, Jacqueline Bentel, Richard J.N. Allcock, Tersia Vermeulen, Leslie Calapre, Timothy Isaacs, Melanie R. Ziman, Fred K. Chen, Elin S. GrayAbstractAnalysis of specific somatic copy number alterations (SCNAs) using multiplex ligation-dependent probe amplification (MLPA) is routinely used as prognostic test for uveal melanoma (UM). This technique requires relatively large amounts of input DNA, unattainable from many small fine needle aspirate biopsies. Herein we compared the use of MLPA with whole genome amp...
Source: The Journal of Molecular Diagnostics - January 22, 2020 Category: Pathology Source Type: research

An Isothermal, Multiplex Amplification Assay for Detection and Genotyping of Human Papillomaviruses in Formalin-Fixed, Paraffin-Embedded Tissues
Publication date: Available online 22 January 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Yi-Wei Tang, Lorena Lozano, Xin Chen, Troy D. Querec, Nora Katabi, Antonio Moreno-Docón, Hongmei Wang, Daniel Fix, Louise De Brot, Tracy A. McMillen, Ju-Yoon Yoon, Amparo Torroba, Youxiang Wang, Elizabeth R. Unger, Kay J. ParkAbstractRapid and accurate identification of human papillomavirus (HPV) is important for both clinical management and population screening. We performed analytic validation of Atila AmpFire Multiplex HPV assays on formalin-fixed, paraffin-embedded (FFPE) cervix/vulva and oropharynx diagnosti...
Source: The Journal of Molecular Diagnostics - January 22, 2020 Category: Pathology Source Type: research

Junction Location Identifier: Accurate Detection of DNA Fusions in Clinical Sequencing for Precision Oncology
Publication date: Available online 25 December 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Hyun-Tae Shin, Nayoung K.D. Kim, Jae Won Yun, Boram Lee, Sungkyu Kyung, Ki-Wook Lee, Daeun Ryu, Jinho Kim, Joon Seol Bae, Donghyun Park, Yoon-La Choi, Se-Hoon Lee, Myung-Ju Ahn, Keunchil Park, Woong-Yang ParkAccurate detection of genomic fusions by high-throughput sequencing in clinical samples with inadequate tumor purity and formalin-fixed, paraffin-embedded tissue is an essential task in precise oncology. We developed the fusion detection algorithm Junction Location Identifier for optimization of high-depth clinical...
Source: The Journal of Molecular Diagnostics - January 21, 2020 Category: Pathology Source Type: research

Apparently Heterozygous TP53 Pathogenic Variants May Be Blood Limited in Patients Undergoing Hereditary Cancer Panel Testing
Publication date: Available online 24 December 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Jessica L. Mester, Sarah A. Jackson, Kristen Postula, Amy Stettner, Sheila Solomon, Jeffrey Bissonnette, Patricia D. Murphy, Rachel T. Klein, Kathleen S. HruskaHeterozygous (HET) TP53 pathogenic variants (PVs) are associated with Li-Fraumeni syndrome (LFS), a dominantly inherited condition causing high risk for sarcoma, breast, and other cancers. Recent reports described patients without features of LFS and apparently HET TP53 PVs in blood cells but not fibroblasts (FBs), suggesting the variant occurred sporadically du...
Source: The Journal of Molecular Diagnostics - January 11, 2020 Category: Pathology Source Type: research

Concordance of Genomic Alterations by Next-Generation Sequencing in Tumor Tissue versus Cell-Free DNA in Stage I–IV Non–Small Cell Lung Cancer
Publication date: Available online 16 December 2019Source: The Journal of Molecular DiagnosticsAuthor(s): John Jiang, Hans-Peter Adams, Lijing Yao, Stephanie Yaung, Preeti Lal, Aarthi Balasubramanyam, Frederike Fuhlbrück, Nalin Tikoo, Alexander F. Lovejoy, Sebastian Froehler, Li Tai Fang, H. Jost Achenbach, Ralph Floegel, Rainer Krügel, John PalmaMolecular biomarkers hold promise for personalization of cancer treatment. However, a typical tumor biopsy may be difficult to acquire and may not capture genetic variations within or across tumors. Given these limitations, tumor genotyping using next-generation sequenci...
Source: The Journal of Molecular Diagnostics - December 28, 2019 Category: Pathology Source Type: research

Development and Analytical Validation of a DNA Dual-Strand Approach for the US Food and Drug Administration–Approved Next-Generation Sequencing–Based Praxis Extended RAS Panel for Metastatic Colorectal Cancer Samples
In conclusion, this assay can clearly distinguish single-stranded artifacts from low-frequency mutations. Furthermore, the assay is accurate, precise, and reproducible, can achieve consistent detection of a mutation at 5% mutation frequency, exhibits minimal impact from tested interfering substances, and can simultaneously detect 56 mutations in a single run using 10 samples plus controls. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - December 25, 2019 Category: Pathology Source Type: research

Development and Validation of a Novel and Rapid Molecular Detection Method for High-Risk Human Papillomavirus in Formalin-Fixed Paraffin-Embedded Tumor Tissue
In conclusion, our method is rapid, simple, and shows an excellent diagnostic performance for detection of HPV type 16. Ultimately, it can be applied for large cohort studies to determine the etiologic fraction and prognostic implication of HPV in nonoropharyngeal HNSCC. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - December 25, 2019 Category: Pathology Source Type: research

Apparently Heterozygous TP53 Pathogenic Variants May Be Blood-Limited in Patients Undergoing Hereditary Cancer Panel Testing
Publication date: Available online 24 December 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Jessica L. Mester, Sarah A. Jackson, Kristen Postula, Amy Stettner, Sheila Solomon, Jeffrey Bissonnette, Patricia D. Murphy, Rachel T. Klein, Kathleen S. HruskaABSTRACTHeterozygous (HET) TP53 pathogenic variants (PV) are associated with Li-Fraumeni syndrome (LFS), a dominantly inherited condition causing high risk for sarcoma, breast, and other cancers. Recent reports have described patients without features of LFS and apparently HET TP53 PV in blood cells but not fibroblasts (FB), suggesting the variant occurred spora...
Source: The Journal of Molecular Diagnostics - December 25, 2019 Category: Pathology Source Type: research

Reliable Clinical MLH1 Promoter Hypermethylation Assessment using a High-Throughput Genome-Wide Methylation Array Platform
Publication date: Available online 24 December 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Jamal K. Benhamida, Jaclyn F. Hechtman, Khedoudja Nafa, Liliana Villafania, Justyna Sadowska, Jiajing Wang, Donna Wong, Ahmet Zehir, Liying Zhang, Tejus Bale, Maria E. Arcila, Marc LadanyiAbstractClinical testing for MLH1 promoter hypermethylation status is important in the workup of patients with MLH1-deficient colorectal and uterine carcinomas when evaluating patients for Lynch Syndrome. Current assays utilize single gene–based methods to assess promoter hypermethylation. Herein, we describe the development, an...
Source: The Journal of Molecular Diagnostics - December 25, 2019 Category: Pathology Source Type: research

Clinical performance of the Idylla MSI Test for a rapid assessment of the DNA microsatellite status in human colorectal cancer
In this study we evaluated the clinical performance of the Idylla MSI Test (Investigational Use Only) in 330 colorectal carcinoma samples (all stages). This test is fully automated from formalin-fixed, paraffin-embedded slide to result, and gives a result in less than 2.5 hours. Compared to the Promega MSI Analysis System, Version 1.2, an overall agreement, sensitivity, and specificity of 99.7%, 98.7%, and 100% was reached, respectively. Whereas seven samples were invalid with the Promega MSI Analysis, only two were invalid with the Idylla MSI Test. Compared to the historical immunohistochemistry (IHC) data, an overall agr...
Source: The Journal of Molecular Diagnostics - December 25, 2019 Category: Pathology Source Type: research

JuLI: accurate detection of DNA fusions in clinical sequencing for precision oncology
Publication date: Available online 25 December 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Hyun-Tae Shin, Nayoung K.D. Kim, Jae Won Yun, Boram Lee, Sungkyu Kyung, Ki-Wook Lee, Daeun Ryu, Jinho Kim, Joon Seol Bae, Donghyun Park, Yoon-La Choi, Se-Hoon Lee, Myung-Ju Ahn, Keunchil Park, Woong-Yang ParkAbstractAccurate detection of genomic fusions by high-throughput sequencing in clinical samples with inadequate tumor purity and formalin-fixed, paraffin embedded tissue is an essential task in precise oncology. We developed the fusion detection algorithm Junction Location Identifier for optimization of high-depth ...
Source: The Journal of Molecular Diagnostics - December 25, 2019 Category: Pathology Source Type: research

Validation of an in vitro mismatch repair assay used in the functional characterization of mismatch repair variants
Publication date: Available online 25 December 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Maribel González-Acosta, Inga Hinrichsen, Anna Fernández, Conxi Lázaro, Marta Pineda, Guido Plotz, Gabriel CapelláAbstractA significant proportion of DNA mismatch repair (MMR) variants are classified as of unknown significance (VUS), precluding diagnosis. The in vitro MMR assay is used to assess their MMR capability, likely the most important function of a MMR protein. However, robustness of the assay, critical for its use in the clinical setting, has been rarely evaluated. The aim of the pr...
Source: The Journal of Molecular Diagnostics - December 25, 2019 Category: Pathology Source Type: research

Digital Rolling Circle Amplification–Based Detection of Ebola and Other Tropical Viruses
Publication date: Available online 16 December 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Sibel Ciftci, Felix Neumann, Samir Abdurahman, K. Sofia Appelberg, Ali Mirazimi, Mats Nilsson, Narayanan MadaboosiEmerging tropical viruses have caused serious outbreaks during the recent years, such as Ebola virus (EBOV) in 2014 and the most recent in 2018 to 2019 in Congo. Thus, immediate diagnostic attention is demanded at the point of care in resource-limited settings, because the performance and the operational parameters of conventional EBOV testing are limited. Especially, their sensitivity, specificity, and cov...
Source: The Journal of Molecular Diagnostics - December 24, 2019 Category: Pathology Source Type: research

Multi-Institutional Evaluation of Interrater Agreement of Variant Classification Based on the 2017 Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer
This study demonstrates noteworthy discordances between pathologists for variant classification in solid tumors when using the 2017 Association for Molecular Pathology/American Society of Clinical Oncology/College of American Pathologists guidelines. These findings highlight potential areas for clarification/refinement before mainstream clinical adoption. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - December 24, 2019 Category: Pathology Source Type: research

Digital Gene Expression Analysis on Cytology Smears Can Rule Out Malignancy in Follicular-Patterned Thyroid Tumors
Publication date: Available online 18 November 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Elisabetta Macerola, Anello Marcello Poma, Agnese Proietti, Rossana Romani, Liborio Torregrossa, Clara Ugolini, Teresa Rago, Paolo Vitti, Fulvio BasoloPatients with indeterminate thyroid nodules (Bethesda III and IV) are often treated with diagnostic lobectomy, which in most cases represents an overtreatment. A reliable rule-out molecular test could spare patients unnecessary surgery. Stained smears of 88 indeterminate thyroid nodules with histologic diagnosis of follicular-patterned tumors were selected: 34 follicular...
Source: The Journal of Molecular Diagnostics - December 21, 2019 Category: Pathology Source Type: research

Subgroup Analysis Can Optimize the Relapse-Prediction Cutoff Value for WT1 Expression After Allogeneic Hematologic Stem Cell Transplantation in Acute Myeloid Leukemia
Publication date: Available online 18 November 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Ya-Zhen Qin, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Xiao-Su Zhao, Kai-Yan Liu, Xiao-Jun HuangHigh WT1 expression after allogeneic hematologic stem cell transplantation (allo-HSCT) can strongly predict relapse in acute myeloid leukemia (AML). However, the cutoff values obtained have been inconsistent. Precise cutoff values may be optimized through subtype analysis; the RUNX1-RUNX1T1 fusion transcript provides an ideal reference. RUNX1-RUNX1T1 and WT1 transcript levels were simultaneously measured in 1299 bone marrow samp...
Source: The Journal of Molecular Diagnostics - December 21, 2019 Category: Pathology Source Type: research

Molecular discordance between myeloid sarcomas and concurrent bone marrows occurs in actionable genes and is associated with worse overall survival
Publication date: Available online 19 December 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Brian Werstein, Jennifer Dunlap, Michael J. Cascio, Robert S. Ohgami, Guang Fan, Richard Press, Philipp W. RaessAbstractMyeloid sarcoma is a rare, architecture-effacing proliferation of myeloid blasts localized to an extramedullary site, with or without concurrent bone marrow involvement. Clonal heterogeneity results from acquisition of somatic mutations within different subclones of leukemic cells. We hypothesized that clonal heterogeneity between myeloid sarcomas and concurrent bone marrow biopsies might be present g...
Source: The Journal of Molecular Diagnostics - December 21, 2019 Category: Pathology Source Type: research

Validation of Fragile X Screening in the Newborn Population Using a Fit-for-Purpose FMR1 PCR Assay System
Publication date: Available online 19 December 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Stacey Lee, Jennifer L. Taylor, Charles Redmond, Andrew Hadd, Jon A. Kemppainen, Brian C. Haynes, Scott Shone, Donald B. Bailey, Gary J. LathamAbstractNewborn screening is designed for pre-symptomatic identification of serious conditions with effective early interventions. Clinical laboratories must perform prospective pilot studies to ensure that the analytical performance and workflow for a given screening test are appropriate. We assessed the potential to screen newborns for fragile X syndrome, a monogenic neurodeve...
Source: The Journal of Molecular Diagnostics - December 21, 2019 Category: Pathology Source Type: research

Development and Analytical Validation of an Expanded Mutation Detection Panel for Next-Generation Sequencing of Thyroid Nodule Aspirates
Publication date: Available online 19 December 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Kenny Kwabena Ablordeppey, Venkata Arun Timmaraju, Joanna Wanmin Song-Yang, Sharon Yaqoob, Christina Narick, Alidad Mireskandari, Sydney David Finkelstein, Gyanendra KumarABSTRACTMolecular analysis is used to evaluate the risk of malignancy for thyroid fine needle aspirates, identified as indeterminate by microscopic cytology, based on the detection of various oncogenic DNA mutations and fusion transcripts, or upon the use of various mRNAs or microRNA-based classifier algorithms. Our approach has been to use a combinat...
Source: The Journal of Molecular Diagnostics - December 21, 2019 Category: Pathology Source Type: research

Instructions to Authors
Publication date: January 2020Source: The Journal of Molecular Diagnostics, Volume 22, Issue 1Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - December 19, 2019 Category: Pathology Source Type: research

Editorial Board
Publication date: January 2020Source: The Journal of Molecular Diagnostics, Volume 22, Issue 1Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - December 19, 2019 Category: Pathology Source Type: research

Table of Contents
Publication date: January 2020Source: The Journal of Molecular Diagnostics, Volume 22, Issue 1Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - December 19, 2019 Category: Pathology Source Type: research

Scientific Integrity Policy
Publication date: January 2020Source: The Journal of Molecular Diagnostics, Volume 22, Issue 1Author(s): (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - December 19, 2019 Category: Pathology Source Type: research

Renewed Commitments to Key Partners
Publication date: January 2020Source: The Journal of Molecular Diagnostics, Volume 22, Issue 1Author(s): Barbara A. Zehnbauer (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - December 19, 2019 Category: Pathology Source Type: research

Clinical Validation of a Myeloid Next-Generations Sequencing Panel for Single-Nucleotide Variants, Insertions/Deletions, and Fusion Genes
In conclusion, the OMR panel is a highly accurate and reproducible next-generation sequencing panel for the detection of common genetic alterations in myeloid neoplasms. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - December 18, 2019 Category: Pathology Source Type: research

Single-Molecule Sequencing: A New Approach for Preimplantation Testing and Noninvasive Prenatal Diagnosis Confirmation of Fetal Genotype
Publication date: Available online 18 November 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Svetlana Rechitsky, Anver Kuliev, Geraldine San Ramon, Ilan Tur-Kaspa, Yin Wang, Wenjie Wang, Xueqing Wu, Li Wang, Don Leigh, David S. CramWe investigated the potential of next-generation sequencing (NGS) as an alternative method for preimplantation genetic testing of monogenic disease (PGT-M) with human leukocyte antigen (HLA) matching and for noninvasive prenatal diagnosis follow-up. The case involved parents who were carriers of the FANCG 260delG mutation. After clinical PGT using conventional STR and mutation analy...
Source: The Journal of Molecular Diagnostics - December 18, 2019 Category: Pathology Source Type: research

Multi-Institutional Evaluation of Inter-rater Agreement of Variant Classification Based on the 2017 AMP, ASCO and CAP Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer
This study demonstrates noteworthy discordances between pathologists for variant classification in solid tumors when using the 2017 AMP/ASCO/CAP guidelines. These findings highlight potential areas for clarification/refinement prior to mainstream clinical adoption. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - December 17, 2019 Category: Pathology Source Type: research