Correction
In the article entitled, “A Clinical Grade Sequencing-Based Assay for CEBPA Mutation Testing: Report of a Large Series of Myeloid Neoplasms” (Volume 17, pages 76–84 of the January 2015 issue of The Journal of Molecular Diagnostics), reference 24 on page 78 was incorrect. The correct citations are as follows: (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 14, 2015 Category: Pathology Tags: Correction Source Type: research

Editorial Board
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 14, 2015 Category: Pathology Source Type: research

Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 14, 2015 Category: Pathology Source Type: research

Reporting Incidental Findings in Genomic Scale Clinical Sequencing—A Clinical Laboratory Perspective
Advances in sequencing technologies have facilitated concurrent testing for many disorders, and the results generated may provide information about a patient's health that is unrelated to the clinical indication, commonly referred to as incidental findings. This is a paradigm shift from traditional genetic testing in which testing and reporting are tailored to a patient's specific clinical condition. Clinical laboratories and physicians are wrestling with this increased complexity in genomic testing and reporting of the incidental findings to patients. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - February 12, 2015 Category: Pathology Authors: Madhuri Hegde, Sherri Bale, Pinar Bayrak-Toydemir, Jane Gibson, Linda Jo Bone Jeng, Loren Joseph, Jordan Laser, Ira M. Lubin, Christine E. Miller, Lainie F. Ross, Paul G. Rothberg, Alice K. Tanner, Patrik Vitazka, Rong Mao Tags: Special article Source Type: research

Relationship between and Variants and the Clinical Phenotype in Late-Onset Cystic Fibrosis Disease with Chronic Pancreatitis
Cystic fibrosis (CF), the most common autosomal recessive disease in whites, is caused by mutations in the CF transmembrane conductance regulator (CFTR). So far,>1900 mutations have been described, most of which are nonsense, missense, and frameshift, and can lead to severe phenotypes, reducing the level of function of the CFTR protein. Synonymous variations are usually considered silent without pathogenic effects. However, synonymous mutations exhibiting exon skipping as a consequence of aberrant splicing of pre-mRNA differ. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - January 27, 2015 Category: Pathology Authors: Anna C. Tomaiuolo, Valentina M. Sofia, Cecilia Surace, Fabio Majo, Silvia Genovese, Stefano Petrocchi, Simona Grotta, Federico Alghisi, Vincenzina Lucidi, Adriano Angioni Tags: Regular Article Source Type: research

NADf Chip, a Two-Color Microarray for Simultaneous Screening of Multigene Mutations Associated with Hearing Impairment in North African Mediterranean Countries
Hearing impairment (HI) is the most frequent sensory defect. Genetic causes are involved in two thirds of prelingual cases. Moreover, the autosomal recessive HI frequency is increased in countries where there is a high rate of consanguinity, such as in North African Mediterranean countries. This population shares several features, including history and social behavior, that promote the spread of founder mutations. HI is characterized by tremendous heterogeneity in both the genetic and clinical aspects. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - January 2, 2015 Category: Pathology Authors: Imen Chakchouk, Mariem Ben Said, Fida Jbeli, Riadh Benmarzoug, Salma Loukil, Ibtihel Smeti, Amine Chakroun, Abdullah Ahmed Yousef Gibriel, Abdelmonem Ghorbel, Hassen Hadjkacem, Saber Masmoudi Tags: Regular Article Source Type: research

Next-Generation Sequencing of the and Genes for the Genetic Diagnostics of Hereditary Breast and/or Ovarian Cancer
Genetic testing for hereditary breast and/or ovarian cancer mostly relies on laborious molecular tools that use Sanger sequencing to scan for mutations in the BRCA1 and BRCA2 genes. We explored a more efficient genetic screening strategy based on next-generation sequencing of the BRCA1 and BRCA2 genes in 210 hereditary breast and/or ovarian cancer patients. We first validated this approach in a cohort of 115 samples with previously known BRCA1 and BRCA2 mutations and polymorphisms. Genomic DNA was amplified using the Ion AmpliSeq BRCA1 and BRCA2 panel. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 31, 2014 Category: Pathology Authors: Daniel Trujillano, Maximilian E.R. Weiss, Juliane Schneider, Julia Köster, Efstathios B. Papachristos, Viatcheslav Saviouk, Tetyana Zakharkina, Nahid Nahavandi, Lejla Kovacevic, Arndt Rolfs Tags: Regular Article Source Type: research

miR-210 Is a Prognostic Marker in Clear Cell Renal Cell Carcinoma
Accurate assessment of prognosis of clear cell renal cell carcinoma (ccRCC) is key in optimizing management plans to fit individual patient needs. miRNAs are short noncoding single-stranded RNAs that control the expression of target genes and may act as cancer biomarkers. We analyzed the expression of miR-210 in 276 cases of primary ccRCC and compared its expression in 40 pairs of adjacent normal and cancerous tissues. We assessed its expression in primary and metastatic tumors, in the common RCC subtypes, and the benign oncocytoma. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 30, 2014 Category: Pathology Authors: Sara Samaan, Heba W.Z. Khella, Andrew Girgis, Andreas Scorilas, Evi Lianidou, Manal Gabril, Sergey N. Krylov, Michael Jewett, Georg A. Bjarnason, Hala El-said, George M. Yousef Tags: Regular Article Source Type: research

A DNA Real-Time Quantitative PCR Method Suitable for Routine Monitoring of Low Levels of Minimal Residual Disease in Chronic Myeloid Leukemia
The BCR-ABL1 sequence has advantages over the BCR-ABL1 transcript as a molecular marker in chronic myeloid leukemia and has been used in research studies. We developed a DNA real-time quantitative PCR (qPCR) method for quantification of BCR-ABL1 sequences, which is also potentially suitable for routine use. The BCR-ABL1 breakpoint was sequenced after isolation by nested short-range PCR of DNA from blood, marrow, and cells on slides, obtained either at diagnosis or during treatment, or from artificial mixtures. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 29, 2014 Category: Pathology Authors: Paul A. Bartley, Susan Latham, Bradley Budgen, David M. Ross, Elizabeth Hughes, Susan Branford, Deborah White, Timothy P. Hughes, Alexander A. Morley Tags: Regular article Source Type: research

Two Novel Methods for Rapid Detection and Quantification of R882 Mutations in Acute Myeloid Leukemia
DNMT3A mutations represent one of the most frequent gene alterations detectable in acute myeloid leukemia with normal karyotype. Although various recurrent somatic mutations of DNMT3A have been described, the most common mutation is located at amino acid R882 in the methyltransferase domain of the gene. DNMT3A mutations have been reported to be stable during disease progression and are associated with unfavorable outcome in acute myeloid leukemia patients with normal karyotype. Because of their prognostic significance and high stability during disease evolution, DNMT3A mutations might represent highly informative biomarker...
Source: Journal of Molecular Diagnostics - December 29, 2014 Category: Pathology Authors: Melissa Mancini, Syed Khizer Hasan, Tiziana Ottone, Serena Lavorgna, Claudia Ciardi, Daniela F. Angelini, Francesca Agostini, Adriano Venditti, Francesco Lo-Coco Tags: Regular article Source Type: research

Report of New Haplotype for Gene
The ATP-binding cassette, subfamily C [CFTR/MRP], member 2 (ABCC2) gene is a member of the ATP-binding cassette transporters and is involved in the transport of molecules across cellular membranes. Substrates transported by ABCC2 include antiepileptics, statins, tenofovir, cisplatin, irinotecan, and carbamazepine. Because of the pharmacogenomics implications, we developed a clinical laboratory–developed assay to test for seven variants in the ABCC2 gene: c.3563T>A (p.V1188E, rs17222723), c.1249G>A (p.V417I, rs2273697), c.3972C>T (p.I1324I, rs3740066), c.2302C>T (p.R768W, rs56199535), c.2366C>T (p.S789F...
Source: Journal of Molecular Diagnostics - December 29, 2014 Category: Pathology Authors: Victoria M. Pratt, Brittany N. Beyer, Daniel L. Koller, Todd C. Skaar, David A. Flockhart, Kenneth D. Levy, Gail H. Vance Tags: Regular Article Source Type: research

A DNA Real-time Quantitative PCR Method Suitable for Routine Monitoring of Low Levels of Minimal Residual Disease in Chronic Myeloid Leukemia
The BCR-ABL1 sequence has advantages over the BCR-ABL1 transcript as a molecular marker in chronic myeloid leukemia and has been used in research studies. We developed a DNA real-time quantitative PCR (qPCR) method for quantification of BCR-ABL1 sequences, which is also potentially suitable for routine use. The BCR-ABL1 breakpoint was sequenced after isolation by nested short-range PCR of DNA from blood, marrow, and cells on slides, obtained either at diagnosis or during treatment, or from artificial mixtures. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 29, 2014 Category: Pathology Authors: Paul A. Bartley, Susan Latham, Bradley Budgen, David M. Ross, Elizabeth Hughes, Susan Branford, Deborah White, Timothy P. Hughes, Alexander A. Morley Tags: Regular Article Source Type: research

Two Novel Methods for Rapid Detection and Quantification of R882 Mutations in Acute Myeloid Leukemia
DNMT3A mutations represent one of the most frequent gene alterations detectable in acute myeloid leukemia with normal karyotype. Although various recurrent somatic mutations of DNMT3A have been described, the most common mutation is located at amino acid R882 in the methyltransferase domain of the gene. DNMT3A mutations have been reported to be stable during disease progression and are associated with unfavorable outcome in acute myeloid leukemia patients with normal karyotype. Because of their prognostic significance and high stability during disease evolution, DNMT3A mutations might represent highly informative biomarker...
Source: Journal of Molecular Diagnostics - December 29, 2014 Category: Pathology Authors: Melissa Mancini, Syed Khizer Hasan, Tiziana Ottone, Serena Lavorgna, Claudia Ciardi, Daniela F. Angelini, Francesca Agostini, Adriano Venditti, Francesco Lo-Coco Tags: Regular Article Source Type: research

High-Throughput Sequencing Using the Ion Torrent Personal Genome Machine for Clinical Evaluation of Somatic Hypermutation Status in Chronic Lymphocytic Leukemia
For patients with chronic lymphocytic leukemia, an important prognostic indicator is the somatic hypermutation status of immunoglobulin heavy chain variable region nucleic acid within the clonal cell population. Current clinical assays for this evaluation rely on Sanger sequencing and are complex, such that availability of testing for patients is limited and costly. However, advances in high-throughput sequencing provide an opportunity to improve complex clinical sequencing applications. Our goal was to determine whether high-throughput sequencing technology could reliably perform the sequencing required for somatic hyperm...
Source: Journal of Molecular Diagnostics - December 29, 2014 Category: Pathology Authors: Rebecca McClure, Ming Mai, Scott McClure Tags: Regular Article Source Type: research

Target-Enriched Next-Generation Sequencing Reveals Differences between Primary and Secondary Ovarian Tumors in Formalin-Fixed, Paraffin-Embedded Tissue
Differentiating primary endometrioid or mucinous ovarian tumors from secondary ovarian tumors can be challenging. We compared somatic mutation profiles of primary and secondary ovarian cancers to investigate if these profiles can help diagnose ovarian tumors. Cancer-related genes (n = 115) were screened by target-enriched next-generation sequencing in formalin-fixed, paraffin-embedded tumor tissue from 43 primary endometrioid and mucinous ovarian carcinomas and 28 proven colorectal cancer metastases to the ovary. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 26, 2014 Category: Pathology Authors: Stijn Crobach, Dina Ruano, Ronald van Eijk, Gert Jan Fleuren, Ivonne Minderhout, Ronelle Snowdowne, Carli Tops, Tom van Wezel, Hans Morreau Tags: Regular Article Source Type: research

High-Quality Genotyping Data from Formalin-Fixed, Paraffin-Embedded Tissue on the Drug Metabolizing Enzymes and Transporters Plus Array
The Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus array covers 1936 markers in 231 genes involved in drug metabolism and transport. Blood- and saliva-derived DNA works well on the DMET array, but the utility of DNA from FFPE tissue has not been reported for this array. As the ability to use DNA from FFPE tissue on the array could open the potential for large retrospective sample collections, we examined the performance and reliability of FFPE-derived DNA on the DMET Plus array. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 19, 2014 Category: Pathology Authors: Hanneke I. Vos, Tahar van der Straaten, Marieke J.H. Coenen, Uta Flucke, D. Maroeska W.M. te Loo, Henk-Jan Guchelaar Tags: Technical advance Source Type: research

Latent Tuberculosis
This Commentary highlights the article by Kim et al, which describes an approach for efficient diagnosis and differentiation of Mycobacterium tuberculosis infection. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 19, 2014 Category: Pathology Authors: David H. Persing Tags: Commentary Source Type: research

Diagnostic Performance of a Cytokine and IFN-γ–Induced Chemokine mRNA Assay after –Specific Antigen Stimulation in Whole Blood from Infected Individuals
Interferon (IFN)-γ release assays have limited sensitivity and cannot differentiate between active tuberculosis (TB) disease and latent TB infection (LTBI). Numerous cytokines and regulator factors have been implicated in the pathogenesis and control of Mycobacterium tuberculosis infection. Additional cytokines and chemokines associated with M. tuberculosis infection may improve the performance of IFN-γ release assays. We developed a real-time RT-PCR TaqMan assay for targeting levels of eight human targets [IFN-γ, tumor necrosis factor (TNF)-α, IL-2R, IL-4, IL-10, CXCL9, CXCL10, and CXCL11] and eval...
Source: Journal of Molecular Diagnostics - December 19, 2014 Category: Pathology Authors: Sunghyun Kim, Hyejon Lee, Hyunjung Kim, Yeun Kim, Jang-Eun Cho, Hyunwoo Jin, Dae Yeon Kim, Sang-Jun Ha, Young Ae Kang, Sang-Nae Cho, Hyeyoung Lee Tags: Regular article Source Type: research

Comparison of Custom Capture for Targeted Next-Generation DNA Sequencing
Targeted, capture-based DNA sequencing is a cost-effective method to focus sequencing on a coding region or other customized region of the genome. There are multiple targeted sequencing methods available, but none has been systematically investigated and compared. We evaluated four commercially available custom-targeted DNA technologies for next-generation sequencing with respect to on-target sequencing, uniformity, and ability to detect single-nucleotide variations (SNVs) and copy number variations. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 19, 2014 Category: Pathology Authors: Eric Samorodnitsky, Jharna Datta, Benjamin M. Jewell, Raffi Hagopian, Jharna Miya, Michele R. Wing, Senthilkumar Damodaran, Juliana M. Lippus, Julie W. Reeser, Darshna Bhatt, Cynthia D. Timmers, Sameek Roychowdhury Tags: Regular article Source Type: research

Editorial Board
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 19, 2014 Category: Pathology Source Type: research

Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 19, 2014 Category: Pathology Source Type: research

Continuing Excellence
This Editorial introduces new Editor-in-Chief Barbara A Zehnbauer and describes her vision for The Journal of Molecular Diagnostics. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 19, 2014 Category: Pathology Authors: Barbara A. Zehnbauer Tags: Editorial Source Type: research

Instructions to Authors
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 19, 2014 Category: Pathology Source Type: research

Scientific Integrity Policy
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - December 19, 2014 Category: Pathology Source Type: research

Assessing Copy Number Alterations in Targeted, Amplicon-Based Next-Generation Sequencing Data
In this study, we developed an algorithm for detecting CNAs in amplicon-based sequencing data. CNAs determined from the algorithm mirrored those from a hybridization-capture library. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 7, 2014 Category: Pathology Authors: Catherine Grasso, Timothy Butler, Katherine Rhodes, Michael Quist, Tanaya L. Neff, Stephen Moore, Scott A. Tomlins, Erica Reinig, Carol Beadling, Mark Andersen, Christopher L. Corless Tags: Regular Article Source Type: research

Molecular Classification of MYC-Driven B-Cell Lymphomas by Targeted Gene Expression Profiling of Fixed Biopsy Specimens
Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) are aggressive tumors of mature B cells that are distinguished by a combination of histomorphological, phenotypic, and genetic features. A subset of B-cell lymphomas, however, has one or more characteristics that overlap BL and DLBCL, and are categorized as B-cell lymphoma unclassifiable, with features intermediate between BL and DLBCL (BCL-U). Molecular analyses support the concept that there is a biological continuum between BL and DLBCL that includes variable activity of MYC, an oncoprotein once thought to be only associated with BL, but now recognized as a...
Source: Journal of Molecular Diagnostics - November 7, 2014 Category: Pathology Authors: Christopher D. Carey, Daniel Gusenleitner, Bjoern Chapuy, Alexandra E. Kovach, Michael J. Kluk, Heather H. Sun, Rachel E. Crossland, Chris M. Bacon, Vikki Rand, Paola D. Cin, Long P. Le, Donna Neuberg, Aliyah R. Sohani, Margaret A. Shipp, Stefano Monti, S Tags: Regular Article Source Type: research

A Clinical Grade Sequencing-Based Assay for Mutation Testing
Diagnostic testing for CEBPA mutations is the standard of care for cytogenetically normal acute myeloid leukemia. Widespread implementation of this testing is hampered by technical challenges associated with the GC content of the gene, the variability of the mutations, and the complexity of the sequence analysis and variant interpretation. We developed a robust Sanger-sequencing test to detect CEBPA mutations in diagnostic acute myeloid leukemia specimens. Our experience with testing 2393 cases of suspected myeloid neoplasms is presented. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 5, 2014 Category: Pathology Authors: Amir Behdad, Helmut C. Weigelin, Kojo S.J. Elenitoba-Johnson, Bryan L. Betz Tags: Regular article Source Type: research

A Clinical Grade Sequencing-Based Assay for Mutation Testing: Report of a Large Series of Myeloid Neoplasms
Diagnostic testing for CEBPA mutations is the standard of care for cytogenetically normal acute myeloid leukemia. Widespread implementation of this testing is hampered by technical challenges associated with the GC content of the gene, the variability of the mutations, and the complexity of the sequence analysis and variant interpretation. We developed a robust Sanger-sequencing test to detect CEBPA mutations in diagnostic acute myeloid leukemia specimens. Our experience with testing 2393 cases of suspected myeloid neoplasms is presented. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 5, 2014 Category: Pathology Authors: Amir Behdad, Helmut C. Weigelin, Kojo S.J. Elenitoba-Johnson, Bryan L. Betz Tags: Regular Article Source Type: research

Extra Alleles in Triple-Primed PCR
The objectives of this study were to determine the cause of these extra peaks; to identify whether these peaks represent an assay specific artifact, an underlying chromosome aneuploidy, or somatic mosaicism; and to ascertain their clinical relevance. The presence of an extra allele(s) was confirmed by a laboratory-developed PCR, with sequencing of the FMR1 5′ UTR or Southern blot for some samples. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 1, 2014 Category: Pathology Authors: Erin N. Wakeling, Fatimah A. Nahhas, Gerald L. Feldman Tags: Regular article Source Type: research

Seven Novel Probe Systems for Real-Time PCR Provide Absolute Single-Base Discrimination, Higher Signaling, and Generic Components
We have developed novel probe systems for real-time PCR that provide higher specificity, greater sensitivity, and lower cost relative to dual-labeled probes. The seven DNA Detection Switch (DDS)-probe systems reported here employ two interacting polynucleotide components: a fluorescently labeled probe and a quencher antiprobe. High-fidelity detection is achieved with three DDS designs: two internal probes (internal DDS and Flip probes) and a primer probe (ZIPR probe), wherein each probe is combined with a carefully engineered, slightly mismatched, error-checking antiprobe. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 1, 2014 Category: Pathology Authors: James L. Murray, Peixu Hu, David A. Shafer Tags: Regular article Source Type: research

On to the Next Phase of Molecular Diagnostics—The Ultimate Laboratory Test
This Guest Editorial celebrates the 20th Anniversary of the Annual Meeting of the Association for Molecular Pathology. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 1, 2014 Category: Pathology Authors: Daniel H. Farkas Tags: Guest editorial Source Type: research

Truncating Variants in the Majority of the Cytoplasmic Domain of Are Unlikely to Cause Usher Syndrome 1F
Loss of function variants in the PCDH15 gene can cause Usher syndrome type 1F, an autosomal recessive disease associated with profound congenital hearing loss, vestibular dysfunction, and retinitis pigmentosa. The Ashkenazi Jewish population has an increased incidence of Usher syndrome type 1F (founder variant p.Arg245X accounts for 75% of alleles), yet the variant spectrum in a panethnic population remains undetermined. We sequenced the coding region and intron-exon borders of PCDH15 using next-generation DNA sequencing technology in approximately 14,000 patients from fertility clinics. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 1, 2014 Category: Pathology Authors: Cynthia Perreault-Micale, Alexander Frieden, Caleb J. Kennedy, Dana Neitzel, Jessica Sullivan, Nicole Faulkner, Stephanie Hallam, Valerie Greger Tags: Regular article Source Type: research

Reflecting on My Time as Editor-in-Chief
In his farewell Editorial, Dr. O'Leary reflects fondly on his term as Editor-in Chief of The Journal of Molecular Diagnostics. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 1, 2014 Category: Pathology Authors: Timothy J. O'Leary Tags: Editorial Source Type: research

Regulating Laboratory-Developed Tests
This Editorial provides a perspective on the US Food and Drug Administration's proposed guidance on laboratory developed tests. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 1, 2014 Category: Pathology Authors: Timothy J. O'Leary Tags: Editorial Source Type: research

Editorial Board
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 1, 2014 Category: Pathology Source Type: research

Table of Contents
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 1, 2014 Category: Pathology Source Type: research

Title Page
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 1, 2014 Category: Pathology Source Type: research

Abstract Disclosures
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 1, 2014 Category: Pathology Source Type: research

Abstracts
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 1, 2014 Category: Pathology Source Type: research

Author Index
(Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - November 1, 2014 Category: Pathology Source Type: research

Development of a High-Resolution Melting Curve Analysis Screening Test for Splicing Factor Gene Mutations in Myelodysplastic Syndromes
We describe a high-resolution melting (HRM) curve analysis to screen for SRSF2 hotspot mutations in a fast, sensitive, and reliable way. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 24, 2014 Category: Pathology Authors: Eduardo Garza, Emiliano Fabiani, Nelida Noguera, Paola Panetta, Maria Liliana Piredda, Loredana Borgia, Luca Maurillo, Gianfranco Catalano, Maria Teresa Voso, Francesco Lo-Coco Tags: Regular Article Source Type: research

Diagnostic Application of an Extensive Gene Panel for Leber Congenital Amaurosis with Severe Genetic Heterogeneity
We report results of a diagnostic application of an extensive gene panel composed of 204 retinal dystrophy–related genes and discuss its feasibility as a diagnostic tool. Nineteen unrelated LCA patients were included in the study: two patients for validation purposes of our gene panel, 15 previously analyzed patients with no identified mutations, and two previously unanalyzed patients. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 24, 2014 Category: Pathology Authors: Moon-Woo Seong, Soo Hyun Seo, Young Suk Yu, Jeong-Min Hwang, Sung Im Cho, Eun Kyung Ra, Hyunwoong Park, Seung Jun Lee, Ji Yeon Kim, Sung Sup Park Tags: Regular Article Source Type: research

Simultaneous Detection of Clinically Relevant Mutations and Amplifications for Routine Cancer Pathology
We present a modified version of a multiplexed PCR and IonTorrent-based sequencing approach that can replace a large number of existing assays. The test allows for the simultaneous detection of point mutations and gene amplifications in 40 genes, including known hotspot regions in oncogenes (KRAS, BRAF), inactivating mutations in tumor suppressors (TP53, PTEN), and oncogene amplifications (ERBB2, EGFR). (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 24, 2014 Category: Pathology Authors: Marlous Hoogstraat, John W.J. Hinrichs, Nicolle J.M. Besselink, Joyce H. Radersma-van Loon, Carmen M.A. de Voijs, Ton Peeters, Isaac J. Nijman, Roel A. de Weger, Emile E. Voest, Stefan M. Willems, Edwin Cuppen, Marco J. Koudijs Tags: Technical Advance Source Type: research

Whole-Genome Sequencing Identifies Patient-Specific DNA Minimal Residual Disease Markers in Neuroblastoma
PCR-based detection of minimal residual disease (MRD) in neuroblastoma is currently based on RNA markers; however, expression of these targets can vary, and only paired-like homeobox 2b has no background expression. We investigated whether chromosomal breakpoints, identified by whole-genome sequencing (WGS), can be used as patient-specific DNA MRD markers. WGS data were used to develop large numbers of real-time PCRs specific for tumors of eight patients. These PCRs were used to quantify chromosomal breakpoints in primary tumor and bone marrow samples. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 24, 2014 Category: Pathology Authors: Esther M. van Wezel, Danny Zwijnenburg, Lily Zappeij-Kannegieter, Erik Bus, Max M. van Noesel, Jan J. Molenaar, Rogier Versteeg, Marta Fiocco, Huib N. Caron, C. Ellen van der Schoot, Jan Koster, Godelieve A.M. Tytgat Tags: Regular Article Source Type: research

Assessment of HaloPlex Amplification for Sequence Capture and Massively Parallel Sequencing of Arrhythmogenic Right Ventricular Cardiomyopathy–Associated Genes
The genetic basis of arrhythmogenic right ventricular cardiomyopathy (ARVC) is complex. Mutations in genes encoding components of the cardiac desmosomes have been implicated as being causally related to ARVC. Next-generation sequencing allows parallel sequencing and duplication/deletion analysis of many genes simultaneously, which is appropriate for screening of mutations in disorders with heterogeneous genetic backgrounds. We designed and validated a next-generation sequencing test panel for ARVC using HaloPlex. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - October 24, 2014 Category: Pathology Authors: Anna Gréen, Henrik Gréen, Malin Rehnberg, Anneli Svensson, Cecilia Gunnarsson, Jon Jonasson Tags: Regular Article Source Type: research

Long Noncoding RNAs as Putative Biomarkers for Prostate Cancer Detection
Prostate cancer is one of the leading causes of mortality among US males. There is an urgent unmet need to develop sensitive and specific biomarkers for the early detection of prostate cancer to reduce overtreatment and accompanying morbidity. We identified a group of differentially expressed long noncoding RNAs in prostate cancer cell lines and patient samples and further characterized six long noncoding RNAs (AK024556, XLOC_007697, LOC100287482, XLOC_005327, XLOC_008559, and XLOC_009911) in prostatic adenocarcinoma tissue samples (Gleason score>6.0) and compared them with matched normal (healthy) tissues. (Source: Jou...
Source: Journal of Molecular Diagnostics - October 9, 2014 Category: Pathology Authors: Bongyong Lee, Joseph Mazar, Muhammad N. Aftab, Feng Qi, John Shelley, Jian-Liang Li, Subramaniam Govindarajan, Felipe Valerio, Inoel Rivera, Tadzia Thurn, Tien Anh Tran, Darian Kameh, Vipul Patel, Ranjan J. Perera Tags: Regular article Source Type: research

Molecular Oncology Testing in Resource-Limited Settings
Cancer prevalence and mortality are high in developing nations, where resources for cancer control are inadequate. Nearly one-quarter of cancers in resource-limited nations are infection related, and molecular assays can capitalize on this relationship by detecting pertinent pathogen genomes and human gene variants to identify those at highest risk for progression to cancer, to classify lesions, to predict effective therapy, and to monitor tumor burden over time. Prime examples are human papillomavirus in cervical neoplasia, Helicobacter pylori and Epstein-Barr virus in gastric adenocarcinoma and lymphoma, and hepatitis B ...
Source: Journal of Molecular Diagnostics - September 18, 2014 Category: Pathology Authors: Margaret L. Gulley, Douglas R. Morgan Tags: Review Source Type: research

Alternative Probe-Based Detection Systems in Quantitative PCR
This commentary highlights the article by Murray et al that describes novel probe systems for real-time PCR that provide improvements relative to dual-labeled probes. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - September 18, 2014 Category: Pathology Authors: Douglas R. Storts Tags: Commentary Source Type: research

Comprehensive Diagnostic Testing for Stereocilin
Next-generation sequencing (NGS) technologies have revolutionized genetic testing by enabling simultaneous analysis of unprecedented numbers of genes. However, genes with high-sequence homology pose challenges to current NGS technologies. Because diagnostic sequencing is moving toward exome analysis, knowledge of these homologous genes is essential to avoid false positive and negative results. An example is the STRC gene, one of>70 genes known to contribute to the genetic basis of hearing loss. (Source: Journal of Molecular Diagnostics)
Source: Journal of Molecular Diagnostics - August 22, 2014 Category: Pathology Authors: Diana Mandelker, Sami S. Amr, Trevor Pugh, Sivakumar Gowrisankar, Rimma Shakhbatyan, Elizabeth Duffy, Mark Bowser, Bryan Harrison, Katherine Lafferty, Lisa Mahanta, Heidi L. Rehm, Birgit H. Funke Tags: Regular article Source Type: research

Prospective Enterprise-Level Molecular Genotyping of a Cohort of Cancer Patients
Ongoing cancer genome characterization studies continue to elucidate the spectrum of genomic abnormalities that drive many cancers, and in the clinical arena assessment of the driver genetic alterations in patients is playing an increasingly important diagnostic and/or prognostic role for many cancer types. However, the landscape of genomic abnormalities is still unknown for less common cancers, and the influence of specific genotypes on clinical behavior is often still unclear. To address some of these deficiencies, we developed Profile, a prospective cohort study to obtain genomic information on all patients at a large t...
Source: Journal of Molecular Diagnostics - August 22, 2014 Category: Pathology Authors: Laura E. MacConaill, Elizabeth Garcia, Priyanka Shivdasani, Matthew Ducar, Ravali Adusumilli, Marc Breneiser, Mark Byrne, Lawrence Chung, Jodie Conneely, Lauren Crosby, Levi A. Garraway, Xin Gong, William C. Hahn, Charlie Hatton, Philip W. Kantoff, Michae Tags: Regular article Source Type: research