Proteomics

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Functional Proteogenomics Reveals Biomarkers and Therapeutic Targets in Lymphomas

ABSTRACT: The proteomic and posttranslational modification signatures of most cancers are unknown. N-linked glycosylation is a post-translational modification that targets proteins for membrane expression or secretion making this class of proteins attractive cancer biomarkers and therapeutic targets. Using an unbiased mass spectrometry (MS)-based approach we generated a compendium of 1,155 N-linked glycoproteins (2,160 N-glycosites) from 44 human primary lymphomas and malignant lymphoma cell lines. Hierarchical clustering highlighted distinct subtype signatures which included several novel subtype-specific biomarkers. Orthogonal immunologic studies in 671 primary lymphoma tissue biopsies, 36 lymphoma-derived cell lines or 8 patient-derived circulating tumor cell samples corroborated MS-based glycoproteomic data and authenticated selected proteins as tissue biomarkers. Functional targeting using a toxin-conjugated ligand in vitro and RNAi-mediated silencing targeting subtype-specific glycoproteins abrogated lymphoma growth in vivo. Our results demonstrate the utility of global N-glycoproteomics discovery of cancer biomarkers and targets for precision therapeutics.

OTHER RELATED OMICS DATASETS IN: PRJNA321212

INSTRUMENT(S): LTQ Orbitrap XL

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lymphoma Cell Line, Lymph Node, Peripheral Blood Lymphocyte

SUBMITTER: Damian Fermin  

LAB HEAD: Kojo Elenitoba-Johnson

PROVIDER: PXD003469 | Pride | 2017-06-19

REPOSITORIES: Pride

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Dataset's files

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Action DRS
UM_2009_1432a-SUDHL4.mzXML Mzxml
UM_2009_1432a-SUDHL4.tandem.xml Xml
UM_2009_1432b-SUDHL4.mzXML Mzxml
UM_2009_1432b-SUDHL4.tandem.xml Xml
UM_2009_1432c-SUDHL4.mzXML Mzxml
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Publications

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 su  ...[more]

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