Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy
Name
1-s2.0-S0092867420314008-main.pdf
Description
Published version
Size
13.78 MB
Format
Unknown
Checksum (MD5)
1a0eb5ae45f18f477bbae8f43ae1e73e
Author(s)
Krug, Karsten
Jaehnig, Eric J.
Satpathy, Shankha
Blumenberg, Lili
Karpova, Alla
Anurag, Meenakshi
Miles, George
Mertins, Philipp
Geffen, Yifat
Tang, Lauren C.
Date Issued
November 2020
Journal
Cell
Publisher
Elsevier BV
Version
Final published version
Abstract
© 2020 The Authors The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this “proteogenomics” approach was applied to 122 treatment-naive primary breast cancers 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 prediction of CDK4/6 inhibitor responsiveness. Phosphoproteomics 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 clinical investigation of breast cancer through more accurate annotation of targetable pathways and biological features of this remarkably heterogeneous malignancy.
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2020.10.036
