Print Email Facebook Twitter Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer Title Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer Author Michaut, M (External organisation) Chin, SF (External organisation) Majewski, I (External organisation) Severson, TM (External organisation) Bismeijer, T (External organisation) de Koning, L (External organisation) Peeters, JK (External organisation) Schouten, PC (External organisation) Rueda, OM (External organisation) Bosma, AJ (External organisation) Wessels, L.F.A. (TU Delft Pattern Recognition and Bioinformatics; Netherlands Cancer Institute) Date 2016 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. Subject Breast cancerData integrationFunctional clustering To reference this document use: http://resolver.tudelft.nl/uuid:dac87c83-b448-4d46-9fbb-c023b0ed67a3 DOI https://doi.org/10.1038/srep18517 ISSN 2045-2322 Source Scientific Reports, 6, 1-13 Part of collection Institutional Repository Document type journal article Rights © 2016 M Michaut, SF Chin, I Majewski, TM Severson, T Bismeijer, L de Koning, JK Peeters, PC Schouten, OM Rueda, AJ Bosma, L.F.A. Wessels, More Authors Files PDF srep18517_1_.pdf 1.43 MB Close viewer /islandora/object/uuid:dac87c83-b448-4d46-9fbb-c023b0ed67a3/datastream/OBJ/view