University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Medical Biology
  • Medical Biology - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Medical Biology
  • Medical Biology - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    BRCA1-like signature in triple negative breast cancer: Molecular and clinical characterization reveals subgroups with therapeutic potential.

    Thumbnail
    Download
    Published version (1.139Mb)

    Citations
    Scopus
    Web of Science
    Altmetric
    41
    34
    Author
    Severson, TM; Peeters, J; Majewski, I; Michaut, M; Bosma, A; Schouten, PC; Chin, S-F; Pereira, B; Goldgraben, MA; Bismeijer, T; ...
    Date
    2015-10
    Source Title
    Molecular Oncology
    Publisher
    Wiley
    University of Melbourne Author/s
    Majewski, Ian
    Affiliation
    Medical Biology (W.E.H.I.)
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Severson, T. M., Peeters, J., Majewski, I., Michaut, M., Bosma, A., Schouten, P. C., Chin, S. -F., Pereira, B., Goldgraben, M. A., Bismeijer, T., Kluin, R. J. C., Muris, J. J. F., Jirström, K., Kerkhoven, R. M., Wessels, L., Caldas, C., Bernards, R., Simon, I. M. & Linn, S. (2015). BRCA1-like signature in triple negative breast cancer: Molecular and clinical characterization reveals subgroups with therapeutic potential.. Mol Oncol, 9 (8), pp.1528-1538. https://doi.org/10.1016/j.molonc.2015.04.011.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/254782
    DOI
    10.1016/j.molonc.2015.04.011
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528786
    Abstract
    Triple negative (TN) breast cancers make up some 15% of all breast cancers. Approximately 10-15% are mutant for the tumor suppressor, BRCA1. BRCA1 is required for homologous recombination-mediated DNA repair and deficiency results in genomic instability. BRCA1-mutated tumors have a specific pattern of genomic copy number aberrations that can be used to classify tumors as BRCA1-like or non-BRCA1-like. BRCA1 mutation, promoter methylation, BRCA1-like status and genome-wide expression data was determined for 112 TN breast cancer samples with long-term follow-up. Mutation status for 21 known DNA repair genes and PIK3CA was assessed. Gene expression and mutation frequency in BRCA1-like and non-BRCA1-like tumors were compared. Multivariate survival analysis was performed using the Cox proportional hazards model. BRCA1 germline mutation was identified in 10% of patients and 15% of tumors were BRCA1 promoter methylated. Fifty-five percent of tumors classified as BRCA1-like. The functions of genes significantly up-regulated in BRCA1-like tumors included cell cycle and DNA recombination and repair. TP53 was found to be frequently mutated in BRCA1-like (P < 0.05), while PIK3CA was frequently mutated in non-BRCA1-like tumors (P < 0.05). A significant association with worse prognosis was evident for patients with BRCA1-like tumors (adjusted HR = 3.32, 95% CI = 1.30-8.48, P = 0.01). TN tumors can be further divided into two major subgroups, BRCA1-like and non-BRCA1-like with different mutation and expression patterns and prognoses. Based on these molecular patterns, subgroups may be more sensitive to specific targeted agents such as PI3K or PARP inhibitors.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45689]
    • Medical Biology - Research Publications [865]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors