Abstract

Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying their significant cis-effects and distal trans-effects quantified at the RNA, protein, and phosphoprotein levels. Salient observations include the association of point mutations and copy-number alterations with the rewiring of protein interaction networks, and notably, most cancer genes converge toward similar molecular states denoted by sequence-based kinase activity profiles. A correlation between predicted neoantigen burden and measured T cell infiltration suggests potential vulnerabilities for immunotherapies. Patterns of cancer hallmarks vary by polygenic protein abundance ranging from uniform to heterogeneous. Overall, our work demonstrates the value of comprehensive proteogenomics in understanding the functional states of oncogenic drivers and their links to cancer development, surpassing the limitations of studying individual cancer types.

Original languageEnglish
Pages (from-to)3921-3944.e25
JournalCell
Volume186
Issue number18
DOIs
StatePublished - Aug 31 2023

Keywords

  • CPTAC
  • cancer hallmark
  • oncogenic driver
  • pan-cancer
  • phosphoproteomics
  • protein complex
  • proteogenomics
  • proteomics
  • therapeutic target

Fingerprint

Dive into the research topics of 'Pan-cancer proteogenomics connects oncogenic drivers to functional states'. Together they form a unique fingerprint.

Cite this