• Login
    View Item 
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjects

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    Sensitivity of BRCA1/2 testing in high-risk breast/ovarian/male breast cancer families: little contribution of comprehensive RNA/NGS panel testing

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Byers, H
    Wallis, Y
    van Veen, E
    Lalloo, F
    Reay, K
    Smith, P
    Wallace, A
    Bowers, N
    Newman, William G
    Evans, D Gareth R
    Affiliation
    Genomic Medicine, Institute of Human Development, St. Mary's Hospital, Manchester Academic Health Science Centre, Central Manchester Foundation Trust, University of Manchester, Manchester
    Issue Date
    2016
    
    Metadata
    Show full item record
    Abstract
    The sensitivity of testing BRCA1 and BRCA2 remains unresolved as the frequency of deep intronic splicing variants has not been defined in high-risk familial breast/ovarian cancer families. This variant category is reported at significant frequency in other tumour predisposition genes, including NF1 and MSH2. We carried out comprehensive whole gene RNA analysis on 45 high-risk breast/ovary and male breast cancer families with no identified pathogenic variant on exonic sequencing and copy number analysis of BRCA1/2. In addition, we undertook variant screening of a 10-gene high/moderate risk breast/ovarian cancer panel by next-generation sequencing. DNA testing identified the causative variant in 50/56 (89%) breast/ovarian/male breast cancer families with Manchester scores of ≥50 with two variants being confirmed to affect splicing on RNA analysis. RNA sequencing of BRCA1/BRCA2 on 45 individuals from high-risk families identified no deep intronic variants and did not suggest loss of RNA expression as a cause of lost sensitivity. Panel testing in 42 samples identified a known RAD51D variant, a high-risk ATM variant in another breast ovary family and a truncating CHEK2 mutation. Current exonic sequencing and copy number analysis variant detection methods of BRCA1/2 have high sensitivity in high-risk breast/ovarian cancer families. Sequence analysis of RNA does not identify any variants undetected by current analysis of BRCA1/2. However, RNA analysis clarified the pathogenicity of variants of unknown significance detected by current methods. The low diagnostic uplift achieved through sequence analysis of the other known breast/ovarian cancer susceptibility genes indicates that further high-risk genes remain to be identified.European Journal of Human Genetics advance online publication, 8 June 2016; doi:10.1038/ejhg.2016.57.
    Citation
    Sensitivity of BRCA1/2 testing in high-risk breast/ovarian/male breast cancer families: little contribution of comprehensive RNA/NGS panel testing. 2016: Eur J Hum Genet
    Journal
    European Journal of Human Genetics
    URI
    http://hdl.handle.net/10541/617039
    DOI
    10.1038/ejhg.2016.57
    PubMed ID
    27273131
    Type
    Article
    Language
    en
    ISSN
    1476-5438
    ae974a485f413a2113503eed53cd6c53
    10.1038/ejhg.2016.57
    Scopus Count
    Collections
    All Christie Publications

    entitlement

    Related articles

    • Implementation of next-generation sequencing for molecular diagnosis of hereditary breast and ovarian cancer highlights its genetic heterogeneity.
    • Authors: Pinto P, Paulo P, Santos C, Rocha P, Pinto C, Veiga I, Pinheiro M, Peixoto A, Teixeira MR
    • Issue date: 2016 Sep
    • Statewide Retrospective Review of Familial Pancreatic Cancer in Delaware, and Frequency of Genetic Mutations in Pancreatic Cancer Kindreds.
    • Authors: Catts ZA, Baig MK, Milewski B, Keywan C, Guarino M, Petrelli N
    • Issue date: 2016 May
    • Screening of BRCA1/2 deep intronic regions by targeted gene sequencing identifies the first germline BRCA1 variant causing pseudoexon activation in a patient with breast/ovarian cancer.
    • Authors: Montalban G, Bonache S, Moles-Fernández A, Gisbert-Beamud A, Tenés A, Bach V, Carrasco E, López-Fernández A, Stjepanovic N, Balmaña J, Diez O, Gutiérrez-Enríquez S
    • Issue date: 2019 Feb
    • The identification of pathogenic variants in BRCA1/2 negative, high risk, hereditary breast and/or ovarian cancer patients: High frequency of FANCM pathogenic variants.
    • Authors: Schubert S, van Luttikhuizen JL, Auber B, Schmidt G, Hofmann W, Penkert J, Davenport CF, Hille-Betz U, Wendeburg L, Bublitz J, Tauscher M, Hackmann K, Schröck E, Scholz C, Wallaschek H, Schlegelberger B, Illig T, Steinemann D
    • Issue date: 2019 Jun 1
    • Frequency of mutations in BRCA genes and other candidate genes in high-risk probands or probands with breast or ovarian cancer in the Czech Republic.
    • Authors: Riedlova P, Janoutova J, Hermanova B
    • Issue date: 2020 Apr
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.