Prediction of Lung Cancer Histological Types by RT-qPCR Gene Expression in FFPE Specimens
Publication date: July 2013 Source:The Journal of Molecular Diagnostics, Volume 15, Issue 4 Author(s): Matthew D. Wilkerson , Jason M. Schallheim , D. Neil Hayes , Patrick J. Roberts , Roy R.L. Bastien , Michael Mullins , Xiaoying Yin , C. Ryan Miller , Leigh B. Thorne , Katherine B. Geiersbach , Kenneth L. Muldrew , William K. Funkhouser , Cheng Fan , Michele C. Hayward , Steven Bayer , Charles M. Perou , Philip S. Bernard Lung cancer histologic diagnosis is clinically relevant because there are histology-specific treatment indications and contraindications. Histologic diagnosis can be challenging owing to tumor charact...
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors Guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology
Conclusions: The 37 guideline items address 14 subjects, including 15 recommendations (evidence grade A/B). The major recommendations are to use testing for EGFR mutations and ALK fusions to guide patient selection for therapy with an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitor, respectively, in all patients with advanced-stage adenocarcinoma, regardless of sex, race, smoking history, or other clinical risk factors, and to prioritize EGFR and ALK testing over other molecular predictive tests. As scientific discoveries and clinical practice outpace the completion of randomized clini...
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

New Guideline Sets the Ground Rules for Routine Molecular Testing in Non-Small Cell Lung Cancer
Publication date: July 2013 Source:The Journal of Molecular Diagnostics, Volume 15, Issue 4 Author(s): Nathan A. Pennell , Raymond R. TubbsTeaser The guest editorial highlights the new guidelines for selecting lung cancer patients for EGFR and ALK tyrosine kinase ihibitor molecular testing. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Detection and Species Identification of Malaria Parasites by Isothermal tHDA Amplification Directly from Human Blood without Sample Preparation
We report the clinical and analytical performance of an isothermal thermophilic helicase-dependent amplification assay for blood Plasmodium parasite detection and species-level identification. The assay amplifies the 18S rRNA gene fragment of all Plasmodium species and uses a species-specific probe and a pan-malarial probe to definitively identify Plasmodium falciparum from other infectious Plasmodium species. Amplicon-probe hybridization products are detected with a disposable dipstick enclosed in a cassette. With a pan-malarial–positive and P. falciparum–negative result, an additional test is performed to det...
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

BCR-ABL1 RT-qPCR for Monitoring the Molecular Response to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia
Publication date: September 2013 Source:The Journal of Molecular Diagnostics, Volume 15, Issue 5 Author(s): Richard D. Press , Suzanne Kamel-Reid , Daphne Ang The pathognomonic genetic alteration in chronic myeloid leukemia is the formation of the BCR-ABL1 fusion gene, which produces a constitutively active tyrosine kinase that drives leukemic transformation. Targeted tyrosine kinase inhibitor treatment with imatinib, nilotinib, dasatinib, bosutinib, and ponatinib is the cornerstone of modern therapy for this hematologic malignancy. Real-time quantitative RT-PCR (RT-qPCR, also RQ-PCR) of BCR-ABL1 RNA is a necessary labor...
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Molecular Monitoring of Chronic Myeloid Leukemia International Standardization of BCR-ABL1 Quantitation
Publication date: September 2013 Source:The Journal of Molecular Diagnostics, Volume 15, Issue 5 Author(s): ChaoJie Zhen , Y. Lynn Wang The BCR-ABL1 translocation is a hallmark of chronic myeloid leukemia. Because patients treated with imatinib and other tyrosine kinase inhibitors achieve lower levels of detectable disease, quantitation of BCR-ABL1 transcripts with quantitative RT-PCR has become an essential tool in chronic myeloid leukemia monitoring. The prognostic significance of molecular responses was recently established by large-scale clinical trials. Achieving defined levels of BCR-ABL1 on the International Scale...
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

The Role of MGMT Testing in Clinical Practice A Report of the Association for Molecular Pathology
Publication date: September 2013 Source:The Journal of Molecular Diagnostics, Volume 15, Issue 5 Author(s): Milena Cankovic , Marina N. Nikiforova , Matija Snuderl , Adekunle M. Adesina , Neal Lindeman , Patrick Y. Wen , Eudocia Q. Lee Recent advances in modern molecular technologies allow for the examination and measurement of cancer-related genomic changes. The number of molecular tests for evaluation of diagnostic, prognostic, or predictive markers is expected to increase. In recent years, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been firmly established as a biomarker in patients diagnose...
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Abstracts
Publication date: November 2013 Source:The Journal of Molecular Diagnostics, Volume 15, Issue 6 (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Abstract Disclosures
Publication date: November 2013 Source:The Journal of Molecular Diagnostics, Volume 15, Issue 6 (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Automated Multiplexing Quantum Dots in Situ Hybridization Assay for Simultaneous Detection of ERG and PTEN Gene Status in Prostate Cancer
Publication date: November 2013 Source:The Journal of Molecular Diagnostics, Volume 15, Issue 6 Author(s): Wenjun Zhang , Antony Hubbard , Patrick Brunhoeber , Yixin Wang , Lei Tang The photostability and narrow emission spectra of nonorganic quantum dot fluorophores make them desirable detection methods for ultrasensitive and multiplexing in situ hybridization applications to identify genetic aberrances in morphologically preserved clinical tissue specimens. However, robustness and reliability have not been fully investigated for quantum dot fluorophores in situ hybridization applications. We demonstrate the feasibility...
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Comprehensive Mutation Analysis of the CYP21A2 Gene An Efficient Multistep Approach to the Molecular Diagnosis of Congenital Adrenal Hyperplasia
Publication date: November 2013 Source:The Journal of Molecular Diagnostics, Volume 15, Issue 6 Author(s): Zhi Xu , Wuyan Chen , Deborah P. Merke , Nazli B. McDonnell Congenital adrenal hyperplasia, due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder of adrenal steroidogenesis caused by mutations in the CYP21A2 gene. Direct comparison of established and novel methodologies of CYP21A2 genetic analysis in a large cohort representing a wide range of genotypes has not been previously reported. We genotyped a cohort of 129 unrelated patients with 21-OHD, along with 145 available parents, using Souther...
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Laboratory Practice Guidelines for Detecting and Reporting JAK2 and MPL Mutations in Myeloproliferative Neoplasms A Report of the Association for Molecular Pathology
Publication date: November 2013 Source:The Journal of Molecular Diagnostics, Volume 15, Issue 6 Author(s): Jerald Z. Gong , James R. Cook , Timothy C. Greiner , Cyrus Hedvat , Charles E. Hill , Megan S. Lim , Janina A. Longtine , Daniel Sabath , Y. Lynn Wang Recurrent mutations in JAK2 and MPL genes are genetic hallmarks of BCR-ABL1–negative myeloproliferative neoplasms. Detection of JAK2 and MPL mutations has been incorporated into routine diagnostic algorithms for these diseases. This Special Article summarizes results from a nationwide laboratory survey of JAK2 and MPL mutation analysis. Based on the current pra...
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

AMP v Myriad The Supreme Court Gives a Win to Personalized Medicine
Publication date: November 2013 Source:The Journal of Molecular Diagnostics, Volume 15, Issue 6 Author(s): Roger D. KleinTeaser The guest editorial provides perspective to the decision by the Supreme Court of the United States in the case of Association for Molecular Pathology v Myriad Genetics, Inc. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Scientific Integrity Policy
Publication date: January 2014 Source:The Journal of Molecular Diagnostics, Volume 16, Issue 1 (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

A Novel Methylation PCR that Offers Standardized Determination of FMR1 Methylation and CGG Repeat Length without Southern Blot Analysis
This study describes a simple PCR-only workflow (mPCR) to replace SB analysis, that incorporates novel procedural controls, treatment of the DNA in separate control and methylation-sensitive restriction endonuclease reactions, amplification with labeled primers, and two-color amplicon sizing by capillary electrophoresis. mPCR was evaluated in two independent laboratories with 76 residual clinical samples that represented typical and challenging fragile X alleles in both males and females. mPCR enabled superior size resolution and analytical sensitivity for size and methylation mosaicism compared to SB. Full mutation mosaic...
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Revisiting Oversight and Regulation of Molecular-Based Laboratory-Developed Tests A Position Statement of the Association for Molecular Pathology
Publication date: January 2014 Source:The Journal of Molecular Diagnostics, Volume 16, Issue 1 Author(s): Andrea Ferreira-Gonzalez , Rajyasree Emmadi , Stephen P. Day , Robert F. Klees , Jennifer R. Leib , Elaine Lyon , Jan A. Nowak , Victoria M. Pratt , Mary S. Williams , Roger D. Klein Since 2006, the US Food and Drug Administration, Congress, and other policymakers have explored the appropriate way to guarantee the clinical and analytical validity of laboratory-developed tests. In the past, the Association for Molecular Pathology has publicly urged the Food and Drug Administration to exercise caution in implementing r...
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Assessing and Comparing the Performance of Molecular Diagnostic Tests
Publication date: January 2014 Source:The Journal of Molecular Diagnostics, Volume 16, Issue 1 Author(s): Timothy J. O'LearyTeaser This Editorial describes efforts to ensure that the articles appearing in the Journal meet the highest standards of statistical rigor, allowing laboratorians to make good choices on behalf of their patients. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Reviewer Acknowledgment
Publication date: March 2014 Source:The Journal of Molecular Diagnostics, Volume 16, Issue 2 (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Validation for Clinical Use of, and Initial Clinical Experience with, a Novel Approach to Population-Based Carrier Screening using High-Throughput, Next-Generation DNA Sequencing
We describe a next-generation DNA sequencing-based assay capable of reliably screening patient samples in a timely and comprehensive manner. The analytic accuracy in a research setting has been documented. Here, we describe the additional studies performed to ensure the accuracy (analytic validity) and robustness of our assay for use in clinical practice and provide data from our experience offering this testing. Our clinical experience using this approach to screen 11,691 in vitro fertilization patients has identified 449 mutant alleles: 447 in carriers and 2 in an affected individual. In total, we found 87 distinct ...
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

The Genetic Basis and Expanding Role of Molecular Analysis in the Diagnosis, Prognosis, and Therapeutic Design for Myelodysplastic Syndromes
Publication date: March 2014 Source:The Journal of Molecular Diagnostics, Volume 16, Issue 2 Author(s): Grant E. Nybakken , Adam Bagg The myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders of ineffective hematopoiesis that characteristically demonstrate peripheral blood cytopenia, bone marrow hypercellularity, and morphologically defined dysplasia of one or more hematopoietic lineages. Classical metaphase cytogenetics and judicious use of fluorescence in situ hybridization play central roles in the contemporary diagnosis and classification of MDS. An abundance of recent molecular studies are beg...
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Molecular Pathology Curriculum for Medical Laboratory Scientists A Report of the Association for Molecular Pathology Training and Education Committee
Publication date: May 2014 Source:The Journal of Molecular Diagnostics, Volume 16, Issue 3 Author(s): Sara Taylor , Katie M. Bennett , Joshua L. Deignan , Ericka C. Hendrix , Susan M. Orton , Shalini Verma , Ted E. Schutzbank Molecular diagnostics is a rapidly growing specialty in the clinical laboratory assessment of pathology. Educational programs in medical laboratory science and specialized programs in molecular diagnostics must address the training of clinical scientists in molecular diagnostics, but the educational curriculum for this field is not well defined. Moreover, our understanding of underlying genetic cont...
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Methods-Based Proficiency Testing in Molecular Genetic Pathology
Publication date: May 2014 Source:The Journal of Molecular Diagnostics, Volume 16, Issue 3 Author(s): Iris Schrijver , Nazneen Aziz , Lawrence J. Jennings , Carolyn Sue Richards , Karl V. Voelkerding , Karen E. WeckTeaser This Perspectives article describes methods-based proficiency testing (MBPT), the benefits and limitations of MBPT, why the time is right for MBPT in molecular diagnostics, and how MBPT for next-generation sequencing is being developed by the College of American Pathologists. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Detection of Mutations in Myeloid Malignancies through Paired-Sample Analysis of Microdroplet-PCR Deep Sequencing Data
Publication date: September 2014 Source:The Journal of Molecular Diagnostics, Volume 16, Issue 5 Author(s): Donavan T. Cheng , Janice Cheng , Talia N. Mitchell , Aijazuddin Syed , Ahmet Zehir , Nana Yaa T. Mensah , Alifya Oultache , Khedoudja Nafa , Ross L. Levine , Maria E. Arcila , Michael F. Berger , Cyrus V. Hedvat Amplicon-based methods for targeted resequencing of cancer genes have gained traction in the clinic as a strategy for molecular diagnostic testing. An 847-amplicon panel was designed with the RainDance DeepSeq system, covering most exons of 28 genes relevant to acute myeloid leukemia and myeloproliferative...
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Truncating Variants in the Majority of the Cytoplasmic Domain of PCDH15 Are Unlikely to Cause Usher Syndrome 1F
Publication date: November 2014 Source:The Journal of Molecular Diagnostics, Volume 16, Issue 6 Author(s): Cynthia Perreault-Micale , Alexander Frieden , Caleb J. Kennedy , Dana Neitzel , Jessica Sullivan , Nicole Faulkner , Stephanie Hallam , Valerie Greger 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 s...
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Molecular Oncology Testing in Resource-Limited Settings
Publication date: November 2014 Source:The Journal of Molecular Diagnostics, Volume 16, Issue 6 Author(s): Margaret L. Gulley , Douglas R. Morgan 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...
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

On to the Next Phase of Molecular Diagnostics—The Ultimate Laboratory Test In Observance of the 20th Anniversary of the Annual Meeting of the Association for Molecular Pathology
Publication date: November 2014 Source:The Journal of Molecular Diagnostics, Volume 16, Issue 6 Author(s): Daniel H. FarkasTeaser This Guest Editorial celebrates the 20th Anniversary of the Annual Meeting of the Association for Molecular Pathology. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Regulating Laboratory-Developed Tests
Publication date: November 2014 Source:The Journal of Molecular Diagnostics, Volume 16, Issue 6 Author(s): Timothy J. O'LearyTeaser This Editorial provides a perspective on the US Food and Drug Administration's proposed guidance on laboratory developed tests. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research

Reflecting on My Time as Editor-in-Chief
Publication date: November 2014 Source:The Journal of Molecular Diagnostics, Volume 16, Issue 6 Author(s): Timothy J. O'LearyTeaser In his farewell Editorial, Dr. O'Leary reflects fondly on his term as Editor-in Chief of The Journal of Molecular Diagnostics. (Source: The Journal of Molecular Diagnostics)
Source: The Journal of Molecular Diagnostics - November 6, 2014 Category: Pathology Source Type: research