Functional proteogenomics reveals biomarkers and therapeutic targets in lymphomas.

Autor:	Rolland DCM; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104., Basrur V; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109., Jeon YK; Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea., McNeil-Schwalm C; Department of Pediatrics,University of Michigan Medical School, Ann Arbor, MI 48109., Fermin D; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109., Conlon KP; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109., Zhou Y; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104., Ng SY; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215., Tsou CC; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109., Brown NA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109., Thomas DG; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109., Bailey NG; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109., Omenn GS; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109.; Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109.; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109., Nesvizhskii AI; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109.; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109., Root DE; The Broad Institute of Massachusetts Institute of Technology and Harvard Medical School, Boston, MA 02142., Weinstock DM; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215.; The Broad Institute of Massachusetts Institute of Technology and Harvard Medical School, Boston, MA 02142., Faryabi RB; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.; Center for Personalized Diagnostics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104., Lim MS; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; kojo.elenitoba-johnson@uphs.upenn.edu megan.lim@uphs.upenn.edu., Elenitoba-Johnson KSJ; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; kojo.elenitoba-johnson@uphs.upenn.edu megan.lim@uphs.upenn.edu.; Center for Personalized Diagnostics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2017 Jun 20; Vol. 114 (25), pp. 6581-6586. Date of Electronic Publication: 2017 Jun 12.
DOI:	10.1073/pnas.1701263114
Abstrakt:	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. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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