Functional proteogenomics reveals biomarkers and therapeutic targets in lymphomas

Proc Natl Acad Sci U S A. 2017 Jun 20;114(25):6581-6586. doi: 10.1073/pnas.1701263114. Epub 2017 Jun 12.


Identification of biomarkers and therapeutic targets is a critical goal of precision medicine. N-glycoproteins are a particularly attractive class of proteins that constitute potential cancer biomarkers and therapeutic targets for small molecules, antibodies, and cellular therapies. Using mass spectrometry (MS), we generated a compendium of 1,091 N-glycoproteins (from 40 human primary lymphomas and cell lines). Hierarchical clustering revealed distinct subtype signatures that included several subtype-specific biomarkers. Orthogonal immunological studies in 671 primary lymphoma tissue biopsies and 32 lymphoma-derived cell lines corroborated MS data. In anaplastic lymphoma kinase-positive (ALK+) anaplastic large cell lymphoma (ALCL), integration of N-glycoproteomics and transcriptome sequencing revealed an ALK-regulated cytokine/receptor signaling network, including vulnerabilities corroborated by a genome-wide clustered regularly interspaced short palindromic screen. Functional targeting of IL-31 receptor β, an ALCL-enriched and ALK-regulated N-glycoprotein in this network, abrogated ALK+ALCL growth in vitro and in vivo. Our results highlight the utility of functional proteogenomic approaches for discovery of cancer biomarkers and therapeutic targets.

Keywords: CRISPR screen; RNA-seq; biomarkers; lymphoma; proteomics.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Cell Line, Tumor
  • Humans
  • Lymphoma / genetics*
  • Proteogenomics / methods
  • Receptor Protein-Tyrosine Kinases / genetics
  • Signal Transduction / genetics
  • Transcriptome / genetics*


  • Biomarkers, Tumor
  • Receptor Protein-Tyrosine Kinases