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

Michaut, Magali; Chin, Suet-Feung; Majewski, Ian; Severson, Tesa M; Bismeijer, Tycho; de Koning, Leanne; Peeters, Justine K; Schouten, Philip C; Rueda, Oscar M and Bosma, Astrid J, et al. (2016) In Scientific Reports 6.
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;... (More)
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. (Less)
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Scientific Reports
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6
publisher
Nature Publishing Group
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  • pmid:26729235
  • wos:000368253900001
  • scopus:84953278990
ISSN
2045-2322
DOI
10.1038/srep18517
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English
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72d61b84-dc59-4106-9af1-8ec67e4332a2 (old id 8593203)
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http://www.ncbi.nlm.nih.gov/pubmed/26729235?dopt=Abstract
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@article{72d61b84-dc59-4106-9af1-8ec67e4332a2,
  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.},
  articleno    = {18517},
  author       = {Michaut, Magali and Chin, Suet-Feung and Majewski, Ian and Severson, Tesa M and Bismeijer, Tycho and de Koning, Leanne and Peeters, Justine K and Schouten, Philip C and Rueda, Oscar M and Bosma, Astrid J and Tarrant, Finbarr and Fan, Yue and He, Beilei and Xue, Zheng and Mittempergher, Lorenza and Kluin, Roelof J C and Heijmans, Jeroen and Snel, Mireille and Pereira, Bernard and Schlicker, Andreas and Provenzano, Elena and Ali, Hamid Raza and Gaber, Alexander and O'Hurley, Gillian and Lehn, Sophie and Muris, Jettie J F and Wesseling, Jelle and Kay, Elaine and Sammut, Stephen John and Bardwell, Helen A and Barbet, Aurélie S and Bard, Floriane and Lecerf, Caroline and O'Connor, Darran P and Vis, Daniël J and Benes, Cyril H and McDermott, Ultan and Garnett, Mathew J and Simon, Iris M and Jirström, Karin and Dubois, Thierry and Linn, Sabine C and Gallagher, William M and Wessels, Lodewyk F A and Caldas, Carlos and Bernards, Rene},
  issn         = {2045-2322},
  language     = {eng},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.},
  url          = {http://dx.doi.org/10.1038/srep18517},
  volume       = {6},
  year         = {2016},
}