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Breast cancer quantitative proteome and proteogenomic landscape
Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, S-17121 Solna, Sweden..
Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, S-17121 Solna, Sweden..
Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, S-17121 Solna, Sweden.;Cornell Univ, Div Nutrit Sci, Ithaca, NY 14853 USA..
Oslo Univ Hosp, Inst Canc Res, Dept Tumor Biol, N-0424 Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, N-0424 Oslo, Norway..
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2019 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, article id 1600Article in journal (Refereed) Published
Abstract [en]

In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2019. Vol. 10, article id 1600
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Clinical Medicine
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URN: urn:nbn:se:kth:diva-249785DOI: 10.1038/s41467-019-09018-yISI: 000463695400015PubMedID: 30962452Scopus ID: 2-s2.0-85064079271OAI: oai:DiVA.org:kth-249785DiVA, id: diva2:1307626
Note

QC 20190429

Available from: 2019-04-29 Created: 2019-04-29 Last updated: 2019-04-29Bibliographically approved

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Brismar, Hjalmar

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