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    Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.

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    Author
    Michaut, M; Chin, S-F; Majewski, I; Severson, TM; Bismeijer, T; de Koning, L; Peeters, JK; Schouten, PC; Rueda, OM; Bosma, AJ; ...
    Date
    2016-01-05
    Source Title
    Scientific Reports
    Publisher
    Springer Science and Business Media LLC
    University of Melbourne Author/s
    Majewski, Ian
    Affiliation
    Medical Biology (W.E.H.I.)
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Michaut, M., Chin, S. -F., Majewski, I., Severson, T. M., Bismeijer, T., de Koning, L., Peeters, J. K., Schouten, P. C., Rueda, O. M., Bosma, A. J., Tarrant, F., Fan, Y., He, B., Xue, Z., Mittempergher, L., Kluin, R. J. C., Heijmans, J., Snel, M., Pereira, B. ,... Bernards, R. (2016). Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.. Sci Rep, 6 (1), pp.18517-. https://doi.org/10.1038/srep18517.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/254645
    DOI
    10.1038/srep18517
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700448
    Abstract
    Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies.

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