MassIVE MSV000087576

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Proteogenomic Landscape Of Breast Cancer Tumorigenesis And Targeted Therapy

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Description

Karsten Krug, Eric J. Jaehnig, Shankha Satpathy, Lili Blumenberg, Alla Karpova, Meenakshi Anurag et al., (2020) Cell, 183, 1436-1456
DOI: https://doi.org/10.1016/j.cell.2020.10.036

The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Herein this "proteogenomic" approach was applied to 122 treatment-naive primary breast cancers purposely accrued to preserve post-translational modifications, including protein phosphorylation and acetylation. Proteogenomics challenged standard breast cancer diagnoses, provided detailed analysis of the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint therapy and allowed more accurate assessment of Rb status for the prediction of CDK4/6 inhibitor responsiveness. Phosphoproteomic profiles uncovered novel associations between tumor suppressor loss and targetable kinases. Acetylproteome analysis highlighted acetylation on key nuclear proteins involved in the DNA damage response and revealed cross-talk between cytoplasmic and mitochondrial acetylation and metabolism. Our results underscore the potential of proteogenomics for the clinical investigation of breast cancer through more accurate annotation of targetable pathways and biological features of this remarkably heterogeneous malignancy.

Genomic Data for Breast Cancer tumors is available from the NCI Genomic Data Commons (GDC), here
Gene Expression data in GCT file format is available under the metadata section below
Proteomic Data Analysis for Breast Cancer tumors (PSMs and Summary Reports) is available from the CPTAC Common Data Analysis Pipeline (Study S039 Early Data Release), here

[doi:10.25345/C5Z22N] [dataset license: Custom User License]

Keywords: CPTAC

Contact

Principal Investigators:
(in alphabetical order) 		D.R. Mani, Broad Institute of Massachusetts Institute of Technology and Harvard, US
Matthew J. Elliis, Lester and Sue Smith Breast Center and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, United States
Michael A. Gillette, Broad Institute of Massachusetts Institute of Technology and Harvard, US
Steven A. Carr, Broad Institute of MIT and Harvard, United States
Submitting User: ccms
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