The Experts below are selected from a list of 195 Experts worldwide ranked by ideXlab platform

Matthew J Marton - One of the best experts on this subject based on the ideXlab platform.

  • RESEARCH ARTICLE Analytical Validation of AmpliChip p53 Research Test for Archival Human Ovarian FFPE Sections
    2016
    Co-Authors: Matthew J Marton, Andrew R Mcnamara, Michele D. Nikoloff¤a, Jonathan Cheng
    Abstract:

    The p53 tumor suppressor gene (TP53) is reported to be mutated in nearly half of all tumors and plays a central role in genome integrity. Detection of mutations in p53 can be accom-plished by many assays, including the AmpliChip p53 Research Test. The AmpliChip p53 Research Test has been successfully used to determine p53 status in hematologic malig-nancies and fresh frozen solid tissues but there are few reports of using the assay with for-malin fixed, paraffin-embedded (FFPE) tissue. The objective of this study was to describe analytical performance characterization of the AmpliChip p53 Research Test to detect p53 mutations in genomic DNA isolated from archival FFPE human ovarian tumor tissues. Method correlation with sequencing showed 96%mutation-wise agreement and 99 % chip-wise agreement. We furthermore observed 100 % agreement (113/113) of the most preva-lent TP53 mutations. Workflow reproducibility was 96.8 % across 8 samples, with 2 opera-tors, 2 reagent lots and 2 instruments. Section-to-section reproducibility was 100 % for each sample across a 60 μm region of the FFPE block from ovarian tumors. These data indicate that the AmpliChip p53 Research Test is an accurate and reproducible method for detecting mutations in TP53 from archival FFPE human ovarian specimens

  • analytical validation of AmpliChip p53 research test for archival human ovarian ffpe sections
    PLOS ONE, 2015
    Co-Authors: Matthew J Marton, Michele D Nikoloff, Andrew R Mcnamara, Aki Nakao, Jonathan D Cheng
    Abstract:

    The p53 tumor suppressor gene (TP53) is reported to be mutated in nearly half of all tumors and plays a central role in genome integrity. Detection of mutations in p53 can be accomplished by many assays, including the AmpliChip p53 Research Test. The AmpliChip p53 Research Test has been successfully used to determine p53 status in hematologic malignancies and fresh frozen solid tissues but there are few reports of using the assay with formalin fixed, paraffin-embedded (FFPE) tissue. The objective of this study was to describe analytical performance characterization of the AmpliChip p53 Research Test to detect p53 mutations in genomic DNA isolated from archival FFPE human ovarian tumor tissues. Method correlation with sequencing showed 96% mutation-wise agreement and 99% chip-wise agreement. We furthermore observed 100% agreement (113/113) of the most prevalent TP53 mutations. Workflow reproducibility was 96.8% across 8 samples, with 2 operators, 2 reagent lots and 2 instruments. Section-to-section reproducibility was 100% for each sample across a 60 μm region of the FFPE block from ovarian tumors. These data indicate that the AmpliChip p53 Research Test is an accurate and reproducible method for detecting mutations in TP53 from archival FFPE human ovarian specimens.

  • Analytical reproducibility of AmpliChip p53 Research Test mutation calls.
    2015
    Co-Authors: Matthew J Marton, Michele D Nikoloff, Andrew R Mcnamara, Aki Nakao, Jonathan Cheng
    Abstract:

    Analytical reproducibility of AmpliChip p53 Research Test mutation calls.

  • Cohort 2 samples and exon failures for the AmpliChip p53 Research Test and Sanger sequencing.
    2015
    Co-Authors: Matthew J Marton, Michele D Nikoloff, Andrew R Mcnamara, Aki Nakao, Jonathan Cheng
    Abstract:

    Cohort 2 samples and exon failures for the AmpliChip p53 Research Test and Sanger sequencing.

  • The 32 mutations called by both Sanger and the AmpliChip p53 Research Test (Cohort 2).
    2015
    Co-Authors: Matthew J Marton, Michele D Nikoloff, Andrew R Mcnamara, Aki Nakao, Jonathan Cheng
    Abstract:

    The 32 mutations called by both Sanger and the AmpliChip p53 Research Test (Cohort 2).

Michele D Nikoloff - One of the best experts on this subject based on the ideXlab platform.

Jonathan D Cheng - One of the best experts on this subject based on the ideXlab platform.

  • analytical validation of AmpliChip p53 research test for archival human ovarian ffpe sections
    PLOS ONE, 2015
    Co-Authors: Matthew J Marton, Michele D Nikoloff, Andrew R Mcnamara, Aki Nakao, Jonathan D Cheng
    Abstract:

    The p53 tumor suppressor gene (TP53) is reported to be mutated in nearly half of all tumors and plays a central role in genome integrity. Detection of mutations in p53 can be accomplished by many assays, including the AmpliChip p53 Research Test. The AmpliChip p53 Research Test has been successfully used to determine p53 status in hematologic malignancies and fresh frozen solid tissues but there are few reports of using the assay with formalin fixed, paraffin-embedded (FFPE) tissue. The objective of this study was to describe analytical performance characterization of the AmpliChip p53 Research Test to detect p53 mutations in genomic DNA isolated from archival FFPE human ovarian tumor tissues. Method correlation with sequencing showed 96% mutation-wise agreement and 99% chip-wise agreement. We furthermore observed 100% agreement (113/113) of the most prevalent TP53 mutations. Workflow reproducibility was 96.8% across 8 samples, with 2 operators, 2 reagent lots and 2 instruments. Section-to-section reproducibility was 100% for each sample across a 60 μm region of the FFPE block from ovarian tumors. These data indicate that the AmpliChip p53 Research Test is an accurate and reproducible method for detecting mutations in TP53 from archival FFPE human ovarian specimens.

Jose De Leon - One of the best experts on this subject based on the ideXlab platform.

  • dna microarray technology in the clinical environment the AmpliChip cyp450 test for cyp2d6 and cyp2c19 genotyping
    Cns Spectrums, 2009
    Co-Authors: Jose De Leon, Margaret T Susce, Maria Johnson, Mike Hardin, Alison Shao, Antonette C P Allen, Francis A Chiafari, Grantland Hillman, Michele D Nikoloff
    Abstract:

    Introduction: An important technological advance in genetic testing is the DNA microarray, which allows for the simultaneous testing of thousands of DNA sequences. The AmpliChip CYP450 Test employs this microarray technology for cytochrome P450 (CYP) 2D6 and CYP2C19 genotyping. Isoenzymes encoded by these genes are responsible for the metabolism of many widely prescribed drugs. The objectives of this study were to identify CYP2D6 and CYP2C19 alleles and phenotypes in a psychiatric patient population in Kentucky, and to describe practical issues associated with DNA microarray technology. Methods: A total of 4,532 psychiatric patients were recruited from three state hospitals in Kentucky. Whole blood, buccal swabs, or saliva samples were genotyped with the AmpliChip CYP450 Test to derive a predicted phenotype. Results: In this cohort, the overall prevalence of CYP2D6 poor metabolizers was 7.6% (95% CI 7%, 8.3%), 8.2% in the Caucasians (95% CI 7.4%, 9.1%) and 1.8% in the African Americans (95% CI 0.9%, 3.5%). The overall prevalence of CYP2D6 ultrarapid metabolizers was 1.5% (95% CI 1.2%, 1.9%), 1.5% in the Caucasians (95% CI 1.1%, 1.9%) and 2.0% in the African Americans (95% CI 1.1%, 3.7%). The overall prevalence of CYP2C19 poor metabolizers was 2.0% (95% CI 1.8%, 2.7%), 2.2% in Caucasians (95% CI 1.6%, 2.5%) and 4.0% in African Americans (95% CI 2.6%, 6.1%). Conclusion: We also propose a numeric system for expression of CYP2D6 and CYP2C19 enzyme activity to aid clinicians in determining treatment strategy for patients receiving therapeutics that are metabolized by the CYP2D6 or CYP2C19 gene products.

  • pharmacogenetic testing in psychiatry a review of features and clinical realities
    Clinics in Laboratory Medicine, 2008
    Co-Authors: Jose De Leon, Maria Arranz, Gualberto Ruano
    Abstract:

    This article focuses on the first generation of pharmacogenetic tests that are potentially useful in psychiatry. All pharmacogenetic tests currently on the market, or soon to be marketed in psychiatry, for which some information has been published in peer-reviewed journal articles (or abstracts), were selected. Five pharmacogenetic tests are reviewed in detail: the Roche AmpliChip CYP450 Test, the Luminex Tag-It Mutation Detection Kit, the LGC clozapine response test, the PGxPredict: Clozapine test, and the Genomas PhyzioType system. After reviewing these tests, three practical aspects of implementing pharmacogenetic testing in psychiatric clinical practice are briefly reviewed: (1) the evaluation of these tests in clinical practice, (2) cost-effectiveness, and (3) regulatory oversight. Finally, the future of these and other pharmacogenetic tests in psychiatry is discussed.

  • AmpliChip cyp450 test personalized medicine has arrived in psychiatry
    Expert Review of Molecular Diagnostics, 2006
    Co-Authors: Jose De Leon
    Abstract:

    The US FDA has granted market approval for the first pharmacogenetic test using a DNA microarray, the AmpliChip CYP450, which genotypes cytochrome P450 (CYP)2D6 and CYP2C19. The test uses software to predict phenotypes and tests for 27 CYP2D6 alleles, including the deletions and duplications, and three CYP2C19 alleles. Other DNA microarray platforms are being developed for CYP testing, but none have been completely developed or approved by the FDA to date. The differences between an implementation of pharmacogenetic tests centered on the individual and implementation using a public health approach are discussed. In this review, the major obstacles to the wide implementation of pharmacogenetic testing in the clinical environment are summarized.

  • clinical guidelines for psychiatrists for the use of pharmacogenetic testing for cyp450 2d6 and cyp450 2c19
    Psychosomatics, 2006
    Co-Authors: Jose De Leon, Scott C Armstrong, Kelly L Cozza
    Abstract:

    Pharmacogenetics has arrived in clinical psychiatric practice with the FDA approval of the AmpliChip CYP450 Test that genotypes for two cytochrome P450 2D6 (CYP2D6) and 2C19 (CYP2C19) genes. Other pharmacogenetic tests, including those focused on pharmacodynamic genes, are far from ready for clinical application. CYP2D6 is important for the metabolism of many antidepressants and antipsychotics, and CY2C19 is important for some antidepressant metabolism. Poor metabolizers (PMs), lacking the enzyme, account for up to 7% of Caucasians for CYP2D6 and up to 25% of East Asians for CYP2C19. Patients having three or more active CYP2D6 alleles (up to 29% in North Africa and the Middle East), are called CYP2D6 ultra-rapid metabolizers (UMs). CYP2D6 phenotypes (particularly PMs) are probably important in patients taking tricyclic antidepressants (TCAs), venlafaxine, typical antipsychotics, and risperidone. The CYP2C19 PM phenotype is probably important in patients taking TCAs and perhaps citalopram, escitalopram, and sertraline. On the basis of the literature and the authors' clinical experience, the authors provide provisional recommendations for identifying and treating CYP2D6 PMs, CYP2C19 PMs, and CYP2D6 UMs. The next few years will determine whether CYP2D6 genotyping is beneficial for patients taking the new drugs aripiprazole, duloxetine, and atomoxetine. Practical recommendations for dealing with laboratories offering CYP2D6 and CYP2C29 genotyping are provided.

  • the AmpliChip cyp450 genotyping test integrating a new clinical tool
    Molecular Diagnosis & Therapy, 2006
    Co-Authors: Jose De Leon, Margaret T Susce, Elaina Murraycarmichael
    Abstract:

    The AmpliChip CYP450 Test, which analyzes patient genotypes for cytochrome P450 (CYP) genes CYP2D6 and CYP2C19, is a major step toward introducing personalized prescribing into the clinical environment. Interest in adverse drug reactions (ADRs), the genetic revolution, and pharmacogenetics have converged with the introduction of this tool, which is anticipated to be the first of a new wave of such tools to follow over the next 5-10 years. The AmpliChip CYP450 Test is based on microarray technology, which combines hybridization in precise locations on a glass microarray and a fluorescent labeling system. It classifies individuals into two CYP2C19 phenotypes (extensive metabolizers [EMs] and poor metabolizers [PMs]) by testing three alleles, and into four CYP2D6 phenotypes (ultrarapid metabolizers [UMs], EMs, intermediate metabolizers [IMs], and PMs) by testing 27 alleles, including seven duplications. CYP2D6 is a metabolic enzyme with four activity levels (or phenotypes): UMs with unusually high activity; normal subjects, known as EMs; IMs with low activity; and PMs with no CYP2D6 activity (7% of Caucasians and 1-3% in other ethnic groups). Levels of evidence for the association between CYP2D6 PMs and ADRs are relatively reasonable and include systematic reviews of case-control studies of some typical antipsychotics and tricyclic antidepressants (TCAs). Evidence for other phenotypes is considerably more limited. The CYP2D6 PM phenotype may be associated with risperidone ADRs and discontinuation due to ADRs. Venlafaxine, aripiprazole, duloxetine, and atomoxetine are newer drugs metabolized by CYP2D6 but studies of the clinical relevance of CYP2D6 genotypes are needed. Non-psychiatric drugs metabolized by CYP2D6 include metoprolol, tamoxifen, and codeine-like drugs. CYP2C19 PMs (3-4% of Caucasians and African Americans, and 14-21% of Asians) may require dose adjustment for some TCAs, moclobemide, and citalopram. Other drugs metabolized by CYP2C19 are diazepam and omeprazole. The future of pharmacogenetics depends on the ability to overcome serious obstacles, including the difficulties of conducting and publishing studies in light of resistance from grant agencies, pharmaceutical companies, and some scientific reviewers. Assuming more studies are published, pharmacogenetic clinical applications may be compromised by economic factors and the lack of physician education. The combination of a US FDA-approved test, such as the AmpliChip CYP450 Test, and an FDA definition of CYP2D6 as a 'valid biomarker' makes CYP2D6 genotyping a prime candidate to be the first successful pharmacogenetic test in the clinical environment. One can use microarray technology to test for hundreds of single nucleotide polymorphisms (SNPs) but, taking into account the difficulties for single gene approaches such as CYP2D6, it is unlikely that very complex pharmacogenetic approaches will reach the clinical market in the next 5-10 years.

Andrew R Mcnamara - One of the best experts on this subject based on the ideXlab platform.

  • RESEARCH ARTICLE Analytical Validation of AmpliChip p53 Research Test for Archival Human Ovarian FFPE Sections
    2016
    Co-Authors: Matthew J Marton, Andrew R Mcnamara, Michele D. Nikoloff¤a, Jonathan Cheng
    Abstract:

    The p53 tumor suppressor gene (TP53) is reported to be mutated in nearly half of all tumors and plays a central role in genome integrity. Detection of mutations in p53 can be accom-plished by many assays, including the AmpliChip p53 Research Test. The AmpliChip p53 Research Test has been successfully used to determine p53 status in hematologic malig-nancies and fresh frozen solid tissues but there are few reports of using the assay with for-malin fixed, paraffin-embedded (FFPE) tissue. The objective of this study was to describe analytical performance characterization of the AmpliChip p53 Research Test to detect p53 mutations in genomic DNA isolated from archival FFPE human ovarian tumor tissues. Method correlation with sequencing showed 96%mutation-wise agreement and 99 % chip-wise agreement. We furthermore observed 100 % agreement (113/113) of the most preva-lent TP53 mutations. Workflow reproducibility was 96.8 % across 8 samples, with 2 opera-tors, 2 reagent lots and 2 instruments. Section-to-section reproducibility was 100 % for each sample across a 60 μm region of the FFPE block from ovarian tumors. These data indicate that the AmpliChip p53 Research Test is an accurate and reproducible method for detecting mutations in TP53 from archival FFPE human ovarian specimens

  • analytical validation of AmpliChip p53 research test for archival human ovarian ffpe sections
    PLOS ONE, 2015
    Co-Authors: Matthew J Marton, Michele D Nikoloff, Andrew R Mcnamara, Aki Nakao, Jonathan D Cheng
    Abstract:

    The p53 tumor suppressor gene (TP53) is reported to be mutated in nearly half of all tumors and plays a central role in genome integrity. Detection of mutations in p53 can be accomplished by many assays, including the AmpliChip p53 Research Test. The AmpliChip p53 Research Test has been successfully used to determine p53 status in hematologic malignancies and fresh frozen solid tissues but there are few reports of using the assay with formalin fixed, paraffin-embedded (FFPE) tissue. The objective of this study was to describe analytical performance characterization of the AmpliChip p53 Research Test to detect p53 mutations in genomic DNA isolated from archival FFPE human ovarian tumor tissues. Method correlation with sequencing showed 96% mutation-wise agreement and 99% chip-wise agreement. We furthermore observed 100% agreement (113/113) of the most prevalent TP53 mutations. Workflow reproducibility was 96.8% across 8 samples, with 2 operators, 2 reagent lots and 2 instruments. Section-to-section reproducibility was 100% for each sample across a 60 μm region of the FFPE block from ovarian tumors. These data indicate that the AmpliChip p53 Research Test is an accurate and reproducible method for detecting mutations in TP53 from archival FFPE human ovarian specimens.

  • Analytical reproducibility of AmpliChip p53 Research Test mutation calls.
    2015
    Co-Authors: Matthew J Marton, Michele D Nikoloff, Andrew R Mcnamara, Aki Nakao, Jonathan Cheng
    Abstract:

    Analytical reproducibility of AmpliChip p53 Research Test mutation calls.

  • Cohort 2 samples and exon failures for the AmpliChip p53 Research Test and Sanger sequencing.
    2015
    Co-Authors: Matthew J Marton, Michele D Nikoloff, Andrew R Mcnamara, Aki Nakao, Jonathan Cheng
    Abstract:

    Cohort 2 samples and exon failures for the AmpliChip p53 Research Test and Sanger sequencing.

  • The 32 mutations called by both Sanger and the AmpliChip p53 Research Test (Cohort 2).
    2015
    Co-Authors: Matthew J Marton, Michele D Nikoloff, Andrew R Mcnamara, Aki Nakao, Jonathan Cheng
    Abstract:

    The 32 mutations called by both Sanger and the AmpliChip p53 Research Test (Cohort 2).