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  1. AU="Dominy, Katherine M"
  2. AU="Maunik Chapala"
  3. AU="Luksic, Ivica"
  4. AU="Mastronardi, Luciano"
  5. AU="Md Farijul Islam"
  6. AU="Quansah, Gabriel W"
  7. AU="Keane, Stephen"
  8. AU="Marsela, Enklajd"
  9. AU="Tate, Amanda W"
  10. AU="Solodov, E P"
  11. AU="Cheng-Fang Yen"

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  1. Artikel ; Online: Evaluation of Xpert

    Dominy, Katherine M / Simon, Iris M / Sorouri-Khorashad, Jamshid

    International journal of laboratory hematology

    2020  Band 43, Heft 1, Seite(n) e31–e34

    Mesh-Begriff(e) Fusion Proteins, bcr-abl/genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Neoplasm, Residual/diagnosis ; Neoplasm, Residual/genetics ; Reverse Transcriptase Polymerase Chain Reaction/methods
    Chemische Substanzen Fusion Proteins, bcr-abl (EC 2.7.10.2)
    Sprache Englisch
    Erscheinungsdatum 2020-09-29
    Erscheinungsland England
    Dokumenttyp Letter
    ZDB-ID 2268590-X
    ISSN 1751-553X ; 1751-5521 ; 0141-9854
    ISSN (online) 1751-553X
    ISSN 1751-5521 ; 0141-9854
    DOI 10.1111/ijlh.13348
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  2. Artikel ; Online: Assessment of quantitative polymerase chain reaction for BCR-ABL1 transcripts in chronic myeloid leukaemia: Are improved outcomes in patients with e14a2 transcripts an artefact of technology?

    Dominy, Katherine M / Claudiani, Simone / O'Hare, Matthew / Szydlo, Richard / Gerrard, Gareth / Foskett, Pierre / Foroni, Letizia / Milojkovic, Dragana / Apperley, Jane F / Khorashad, Jamshid

    British journal of haematology

    2022  Band 197, Heft 1, Seite(n) 52–62

    Abstract: The clinical outcome of chronic myeloid leukaemia patients has vastly improved since the introduction of tyrosine kinase inhibitor treatment, with a significant proportion of patients able to achieve treatment-free remission. However, studies have shown ... ...

    Abstract The clinical outcome of chronic myeloid leukaemia patients has vastly improved since the introduction of tyrosine kinase inhibitor treatment, with a significant proportion of patients able to achieve treatment-free remission. However, studies have shown that patients with the e13a2 transcript were less likely to achieve major molecular response compared to those with e14a2 transcripts. Most quantitative polymerase chain reaction (PCR) assays for detection of the BCR-ABL1 fusion gene do not differentiate between the two transcripts and we therefore hypothesised that technical bias linked to the qPCR assay could partially explain the discrepancy in outcomes. We designed an e14a2-specific assay and identified no difference in results compared to an e13a2 standard assay. We then demonstrated that the commercial e14a2 standards were causing a significant overestimation of the e13a2 transcripts. Finally, we reviewed patient management after the qPCR values were corrected, using our new evaluation. We concluded that despite statistically significant differences in qPCR results, there was no impact on patient management or outcome. We conclude that, at least in our institution, it would be inappropriate to perform separate assays for patients with e13a2 or e14a2.
    Mesh-Begriff(e) Fusion Proteins, bcr-abl/genetics ; Humans ; Imatinib Mesylate/therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Real-Time Polymerase Chain Reaction ; Technology
    Chemische Substanzen Imatinib Mesylate (8A1O1M485B) ; Fusion Proteins, bcr-abl (EC 2.7.10.2)
    Sprache Englisch
    Erscheinungsdatum 2022-01-08
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.18026
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Multiplexed color-coded probe-based gene expression assessment for clinical molecular diagnostics in formalin-fixed paraffin-embedded human renal allograft tissue.

    Adam, Benjamin / Afzali, Bahman / Dominy, Katherine M / Chapman, Erin / Gill, Reeda / Hidalgo, Luis G / Roufosse, Candice / Sis, Banu / Mengel, Michael

    Clinical transplantation

    2016  Band 30, Heft 3, Seite(n) 295–305

    Abstract: Histopathologic diagnoses in transplantation can be improved with molecular testing. Preferably, molecular diagnostics should fit into standard-of-care workflows for transplant biopsies, that is, formalin-fixed paraffin-embedded (FFPE) processing. The ... ...

    Abstract Histopathologic diagnoses in transplantation can be improved with molecular testing. Preferably, molecular diagnostics should fit into standard-of-care workflows for transplant biopsies, that is, formalin-fixed paraffin-embedded (FFPE) processing. The NanoString(®) gene expression platform has recently been shown to work with FFPE samples. We aimed to evaluate its methodological robustness and feasibility for gene expression studies in human FFPE renal allograft samples. A literature-derived antibody-mediated rejection (ABMR) 34-gene set, comprised of endothelial, NK cell, and inflammation transcripts, was analyzed in different retrospective biopsy cohorts and showed potential to molecularly discriminate ABMR cases, including FFPE samples. NanoString(®) results were reproducible across a range of RNA input quantities (r = 0.998), with different operators (r = 0.998), and between different reagent lots (r = 0.983). There was moderate correlation between NanoString(®) with FFPE tissue and quantitative reverse transcription polymerase chain reaction (qRT-PCR) with corresponding dedicated fresh-stabilized tissue (r = 0.487). Better overall correlation with histology was observed with NanoString(®) (r = 0.354) than with qRT-PCR (r = 0.146). Our results demonstrate the feasibility of multiplexed gene expression quantification from FFPE renal allograft tissue. This represents a method for prospective and retrospective validation of molecular diagnostics and its adoption in clinical transplantation pathology.
    Mesh-Begriff(e) Allografts ; Biomarkers/analysis ; Fluorescent Dyes ; Follow-Up Studies ; Formaldehyde ; Gene Expression Profiling ; Graft Rejection/diagnosis ; Graft Rejection/epidemiology ; Graft Rejection/genetics ; Humans ; Kidney Transplantation ; Molecular Probe Techniques ; Nanotechnology ; Nucleic Acid Probes ; Organic Chemicals ; Paraffin Embedding ; Pathology, Molecular ; RNA, Messenger/analysis ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Fixation/methods
    Chemische Substanzen Biomarkers ; Fluorescent Dyes ; Nucleic Acid Probes ; Organic Chemicals ; RNA, Messenger ; SYBR Green I (163795-75-3) ; Formaldehyde (1HG84L3525)
    Sprache Englisch
    Erscheinungsdatum 2016-03
    Erscheinungsland Denmark
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639001-8
    ISSN 1399-0012 ; 0902-0063
    ISSN (online) 1399-0012
    ISSN 0902-0063
    DOI 10.1111/ctr.12689
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  4. Artikel ; Online: Molecular Assessment of C4d-Positive Renal Transplant Biopsies Without Evidence of Rejection.

    Dominy, Katherine M / Willicombe, Michelle / Al Johani, Tariq / Beckwith, Hannah / Goodall, Dawn / Brookes, Paul / Cook, H Terence / Cairns, Tom / McLean, Adam / Roufosse, Candice

    Kidney international reports

    2018  Band 4, Heft 1, Seite(n) 148–158

    Abstract: Introduction: Immunohistochemical staining for C4d in peritubular capillaries has been part of antibody-mediated rejection (AbMR) definition in the Banff Classification for Allograft Pathology since 2003. However, it has limited sensitivity and ... ...

    Abstract Introduction: Immunohistochemical staining for C4d in peritubular capillaries has been part of antibody-mediated rejection (AbMR) definition in the Banff Classification for Allograft Pathology since 2003. However, it has limited sensitivity and specificity, therefore the clinical significance of C4d-positive biopsies without evidence of rejection (C4d+ WER) is unknown. We investigated the transcript levels of genes associated with AbMR in C4d+ WER biopsies from both ABO-compatible and incompatible renal transplant patients.
    Methods: RNA was extracted from formalin-fixed paraffin-embedded renal transplant biopsies (
    Results: AbMR-associated transcripts were significantly increased in samples with AbMR or suspicious AbMR. A subgroup of 17 of 35 transcripts that best distinguished AbMR from C4d-negative biopsies without evidence of rejection was used to study C4d+ WER samples. There was no differential expression between C4d-negative and C4d+ WER from both ABO-incompatible and -compatible transplants. The geometric mean of 17 differentially expressed genes was used to assign the C4d+ WER biopsies a high- or low-AbMR transcript score. Follow-up biopsies showed AbMR within 1 year of initial biopsy in 5 of 7 high-AbMR transcript patients but only 2 of 46 low-AbMR transcript patients. In multivariate logistic regression analysis, elevated transcript levels in a C4d+ WER biopsy were associated with increased odds for biopsy-proven AbMR on follow-up (
    Conclusion: Gene expression analysis in C4d+ WER samples has the potential to identify patients at higher risk of developing AbMR.
    Sprache Englisch
    Erscheinungsdatum 2018-09-18
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2468-0249
    ISSN (online) 2468-0249
    DOI 10.1016/j.ekir.2018.09.005
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  5. Artikel ; Online: Use of Quantitative Real Time Polymerase Chain Reaction to Assess Gene Transcripts Associated With Antibody-Mediated Rejection of Kidney Transplants.

    Dominy, Katherine M / Roufosse, Candice / de Kort, Hanneke / Willicombe, Michelle / Brookes, Paul / Behmoaras, Jacques V / Petretto, Enrico G / Galliford, Jack / Choi, Peter / Taube, David / Cook, H Terence / Mclean, Adam G

    Transplantation

    2015  Band 99, Heft 9, Seite(n) 1981–1988

    Abstract: Introduction: Microarray studies have shown elevated transcript levels of endothelial and natural killer (NK) cell-associated genes during antibody-mediated rejection (AMR) of the renal allograft. This study aimed to assess the use of quantitative real- ... ...

    Abstract Introduction: Microarray studies have shown elevated transcript levels of endothelial and natural killer (NK) cell-associated genes during antibody-mediated rejection (AMR) of the renal allograft. This study aimed to assess the use of quantitative real-time polymerase chain reaction as an alternative to microarray analysis on a subset of these elevated genes.
    Methods: Thirty-nine renal transplant biopsies from patients with de novo donor-specific antibodies and eighteen 1-year surveillance biopsies with no histological evidence of rejection were analyzed for expression of 11 genes previously identified as elevated in AMR.
    Results: Expression levels of natural killer markers were correlated to microcirculation inflammation and graft outcomes to a greater extent than endothelial markers. Creating a predictive model reduced the number of gene transcripts to be assessed to 2, SH2D1b and MYBL1, resulting in 66.7% sensitivity and 89.7% specificity for graft loss.
    Discussion: This work demonstrates that elevated gene expression levels, proposed to be associated with AMR, can be detected by established quantitative real-time polymerase chain reaction technology, making transition to the clinical setting feasible. Transcript analysis provides additional diagnostic information to the classification schema for AMR diagnosis but it remains to be determined whether significant numbers of centres will validate transcript analysis in their laboratories and put such analysis into clinical use.
    Mesh-Begriff(e) Biopsy ; Case-Control Studies ; Gene Expression Profiling/methods ; Genetic Markers ; Graft Rejection/genetics ; Graft Rejection/immunology ; Graft Rejection/mortality ; Graft Rejection/pathology ; Graft Survival ; Humans ; Immunity, Humoral/drug effects ; Kaplan-Meier Estimate ; Kidney Transplantation/adverse effects ; Kidney Transplantation/mortality ; Predictive Value of Tests ; Proto-Oncogene Proteins/genetics ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Risk Factors ; Trans-Activators/genetics ; Transcription Factors/genetics ; Transcription, Genetic ; Treatment Outcome
    Chemische Substanzen Genetic Markers ; MYBL1 protein, human ; Proto-Oncogene Proteins ; RNA, Messenger ; SH2D1B protein, human ; Trans-Activators ; Transcription Factors
    Sprache Englisch
    Erscheinungsdatum 2015-02-10
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000000621
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  6. Artikel ; Online: Independent and population-specific association of risk variants at the IRGM locus with Crohn's disease.

    Prescott, Natalie J / Dominy, Katherine M / Kubo, Michiaki / Lewis, Cathryn M / Fisher, Sheila A / Redon, Richard / Huang, Ni / Stranger, Barbara E / Blaszczyk, Katarzyna / Hudspith, Barry / Parkes, Gareth / Hosono, Naoya / Yamazaki, Keiko / Onnie, Clive M / Forbes, Alastair / Dermitzakis, Emmanouil T / Nakamura, Yusuke / Mansfield, John C / Sanderson, Jeremy /
    Hurles, Matthew E / Roberts, Roland G / Mathew, Christopher G

    Human molecular genetics

    2010  Band 19, Heft 9, Seite(n) 1828–1839

    Abstract: DNA polymorphisms in a region on chromosome 5q33.1 which contains two genes, immunity related GTPase related family, M (IRGM) and zinc finger protein 300 (ZNF300), are associated with Crohn's disease (CD). The deleted allele of a 20 kb copy number ... ...

    Abstract DNA polymorphisms in a region on chromosome 5q33.1 which contains two genes, immunity related GTPase related family, M (IRGM) and zinc finger protein 300 (ZNF300), are associated with Crohn's disease (CD). The deleted allele of a 20 kb copy number variation (CNV) upstream of IRGM was recently shown to be in strong linkage disequilibrium (LD) with the CD-associated single nucleotide polymorphisms and is itself associated with CD (P < 0.01). The deletion was correlated with increased or reduced expression of IRGM in transformed cells in a cell line-dependent manner, and has been proposed as a likely causal variant. We report here that small insertion/deletion polymorphisms in the promoter and 5' untranslated region of IRGM are, together with the CNV, strongly associated with CD (P = 1.37 x 10(-5) to 1.40 x 10(-9)), and that the CNV and the 5'-untranslated region variant -308(GTTT)(5) contribute independently to CD susceptibility (P = 2.6 x 10(-7) and P = 2 x 10(-5), respectively). We also show that the CD risk haplotype is associated with a significant decrease in IRGM expression (P < 10(-12)) in untransformed lymphocytes from CD patients. Further analysis of these variants in a Japanese CD case-control sample and of IRGM expression in HapMap populations revealed that neither the IRGM insertion/deletion polymorphisms nor the CNV was associated with CD or with altered IRGM expression in the Asian population. This suggests that the involvement of the IRGM risk haplotype in the pathogenesis of CD requires gene-gene or gene-environment interactions which are absent in Asian populations, or that none of the variants analysed are causal, and that the true causal variants arose after the European-Asian split.
    Mesh-Begriff(e) Asian Continental Ancestry Group/genetics ; Base Sequence ; Crohn Disease/genetics ; DNA Copy Number Variations/genetics ; DNA Primers/genetics ; European Continental Ancestry Group/genetics ; GTP-Binding Proteins/genetics ; GTP-Binding Proteins/metabolism ; Genetic Predisposition to Disease/genetics ; Genetic Variation ; Genotype ; Haplotypes/genetics ; Humans ; INDEL Mutation/genetics ; Logistic Models ; Molecular Sequence Data ; Oligonucleotide Array Sequence Analysis ; Promoter Regions, Genetic/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; United Kingdom
    Chemische Substanzen DNA Primers ; GTP-Binding Proteins (EC 3.6.1.-) ; IRGM protein, human (EC 3.6.1.-)
    Sprache Englisch
    Erscheinungsdatum 2010-01-27
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108742-0
    ISSN 1460-2083 ; 0964-6906
    ISSN (online) 1460-2083
    ISSN 0964-6906
    DOI 10.1093/hmg/ddq041
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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