Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy

Clinical Proteomic Tumor Analysis Consortium

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1436-1456.e31
JournalCell
Volume183
Issue number5
DOIs
StatePublished - Nov 25 2020

Keywords

  • CDK 4/6 inhibitors
  • CPTAC
  • acetylation
  • breast cancer
  • genomics
  • immune checkpoint therapy
  • mass spectrometry
  • phosphoproteomics
  • proteogenomics
  • proteomics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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