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

Chimerism Monitoring after Allogeneic Hematopoietic Stem Cell Transplantation Using Quantitative Real-Time PCR of Biallelic Insertion/Deletion Polymorphisms
An accurate and sensitive determination of chimerism status is mandatory after allogeneic hematopoietic stem cell transplantation. We evaluated the performance of the AlleleSEQR Chimerism Assay, which is based on quantitative real-time PCR of biallelic indel markers, using 79 recipient–donor pairs. When the informativeness of the screening panel composed of 34 markers was determined using 130 unrelated individuals, it presented a>99.9% probability of selecting at least one informative marker. The analytic sensitivity of the indel marker assay was estimated using a serially diluted DNA mixture. (Source: Journal of ...
Source: Journal of Molecular Diagnostics - August 22, 2014 Category: Pathology Authors: Seon Young Kim, Moon Hwan Jeong, Nare Park, Eunkyoung Ra, Hyunwoong Park, Soo Hyun Seo, Ji Yeon Kim, Moon-Woo Seong, Sung Sup Park Tags: Regular article Source Type: research

Altered Interphase Fluorescence Hybridization Profiles of Chromosomes 4, 8q24, and 9q34 in Pancreatic Ductal Adenocarcinoma Are Associated with a Poorer Patient Outcome
Most patients with pancreatic ductal adenocarcinoma (PDAC) die within 6 months of diagnosis. However, 20% to 25% patients undergoing total tumor resection remain alive and disease-free 5 years after diagnostic surgery. Few studies on tumor markers have predicted patient prognosis and/or survival. We evaluated the effect of tumor cytogenetic copy number changes detected by interphase fluorescence in situ hybridization on overall survival (OS) of 55 PDAC patients. The prognostic value of copy number changes showing an effect on OS was validated in an external cohort of 44 surgically resected PDAC patients by comparative geno...
Source: Journal of Molecular Diagnostics - August 22, 2014 Category: Pathology Authors: María L. Gutiérrez, Luis Muñoz-Bellvis, María E. Sarasquete, David G. Hernández-Mejía, María del Mar Abad, Oscar Bengoechea, Luis Corchete, María González-González, Jacinto García-García, Marcos Gonzalez, Ines Mota, Alberto Orfao, José M. Say Tags: Regular article Source Type: research