Functional proteogenomics reveals biomarkers and therapeutic targets in lymphomas [Medical Sciences]
![Functional proteogenomics reveals biomarkers and therapeutic targets in lymphomas [Medical Sciences]](/image/eyJ1cmkiOiJodHRwOi8vd3d3LnBuYXMub3JnL2NvbnRlbnQvZWFybHkvMjAxNy8wNi8wNi8xNzAxMjYzMTE0L0YxLm1lZGl1bS5naWYiLCJmb3JtYXQiOiJ3ZWJwIiwicXVhbGl0eSI6MTAwLCJub0NhY2hlIjp0cnVlfQ==.webp)
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.
Publisher URL: http://feedproxy.google.com/~r/Pnas-RssFeedOfEarlyEditionArticles/~3/13ReLtBNQ4E/1701263114.short
DOI: 10.1073/pnas.1701263114
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