Functional proteogenomics reveals biomarkers and therapeutic targets in lymphomas.
Proc Natl Acad Sci U S A
; 114(25): 6581-6586, 2017 06 20.
Article
em En
| MEDLINE
| ID: mdl-28607076
ABSTRACT
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 ß, 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.
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1
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01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
/
Transcriptoma
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Linfoma
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article