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  • Michaut, Magali (author)

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

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • 2016-01-05
  • Springer Science and Business Media LLC,2016

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:72d61b84-dc59-4106-9af1-8ec67e4332a2
  • https://lup.lub.lu.se/record/8593203URI
  • https://doi.org/10.1038/srep18517DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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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  • Severson, Tesa M (author)
  • Bismeijer, Tycho (author)
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  • Peeters, Justine K (author)
  • Schouten, Philip C (author)
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  • Gaber, AlexanderLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-agb (author)
  • O'Hurley, Gillian (author)
  • Lehn, SophieLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-spl (author)
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  • Sammut, Stephen John (author)
  • Bardwell, Helen A (author)
  • Barbet, Aurélie S (author)
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  • Lecerf, Caroline (author)
  • O'Connor, Darran P (author)
  • Vis, Daniël J (author)
  • Benes, Cyril H (author)
  • McDermott, Ultan (author)
  • Garnett, Mathew J (author)
  • Simon, Iris M (author)
  • Jirström, KarinLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)pat-kji (author)
  • Dubois, Thierry (author)
  • Linn, Sabine C (author)
  • Gallagher, William M (author)
  • Wessels, Lodewyk F A (author)
  • Caldas, Carlos (author)
  • Bernards, Rene (author)
  • TumörmikromiljöSektion I (creator_code:org_t)

Related titles

  • In:Scientific Reports: Springer Science and Business Media LLC62045-2322

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