Breast cancer quantitative proteome and proteogenomic landscape

Henrik J. Johansson, Fabio Socciarelli, Nathaniel M. Vacanti, Mads H. Haugen, Yafeng Zhu, Ioannis Siavelis, Alejandro Fernandez-Woodbridge, Miriam R. Aure, Bengt Sennblad, Mattias Vesterlund, Rui M. Branca, Lukas M. Orre, Mikael Huss, Erik Fredlund, Elsa Beraki, Øystein Garred, Jorrit Boekel, Torill Sauer, Wei Zhao, Silje Nord, Elen K. Höglander, Daniel C. Jans, Hjalmar Brismar, Tonje H. Haukaas, Tone F. Bathen, Ellen Schlichting, Bjørn Naume, Torben Luders, Elin Borgen, Vessela N. Kristensen, Hege G. Russnes, Ole Christian Lingjærde, Gordon B. Mills, Kristine K. Sahlberg, Anne-Lise Børresen-Dale and Janne Lehtiö ()
Additional contact information
Henrik J. Johansson: Karolinska Institutet
Fabio Socciarelli: Karolinska Institutet
Nathaniel M. Vacanti: Karolinska Institutet
Mads H. Haugen: Oslo University Hospital
Yafeng Zhu: Karolinska Institutet
Ioannis Siavelis: Karolinska Institutet
Alejandro Fernandez-Woodbridge: Karolinska Institutet
Miriam R. Aure: Oslo University Hospital
Bengt Sennblad: Uppsala University
Mattias Vesterlund: Karolinska Institutet
Rui M. Branca: Karolinska Institutet
Lukas M. Orre: Karolinska Institutet
Mikael Huss: Stockholm University
Erik Fredlund: Karolinska Institutet
Elsa Beraki: Oslo University Hospital
Øystein Garred: Oslo University Hospital
Jorrit Boekel: Karolinska Institutet
Torill Sauer: Akershus University Hospital
Wei Zhao: The University of Texas MD Anderson Cancer Center
Silje Nord: Oslo University Hospital
Elen K. Höglander: Oslo University Hospital
Daniel C. Jans: KTH Royal Institute of Technology
Hjalmar Brismar: KTH Royal Institute of Technology
Tonje H. Haukaas: The Norwegian University of Science and Technology – NTNU
Tone F. Bathen: The Norwegian University of Science and Technology – NTNU
Ellen Schlichting: Oslo University Hospital
Bjørn Naume: University of Oslo
Torben Luders: University of Oslo
Elin Borgen: Oslo University Hospital
Vessela N. Kristensen: Oslo University Hospital
Hege G. Russnes: Oslo University Hospital
Ole Christian Lingjærde: Oslo University Hospital
Gordon B. Mills: The University of Texas MD Anderson Cancer Center
Kristine K. Sahlberg: Oslo University Hospital
Anne-Lise Børresen-Dale: Oslo University Hospital
Janne Lehtiö: Karolinska Institutet

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-09018-y

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