PXD040718-1

PXD040718 is an original dataset announced via ProteomeXchange.

Title	N-linked glycosylation of the M-protein variable region: Glycoproteogenomics reveals a new layer of personalized complexity in multiple myeloma.
Description	Multiple Myeloma (MM) is a plasma cell malignancy characterized by a monoclonal expansion of plasma cells that secrete a characteristic M-protein. This M-protein is crucial for diagnosis and monitoring of MM in the blood of patients. Recent evidence has emerged that N-glycosylation of the M-protein variable (Fab) region contributes to M-protein pathogenicity, and that it is a risk factor for disease progression of plasma cell disorders. Current methodologies lack the specificity for a site specific glycoprofile of the Fab regions of M-proteins. Here, we introduce a novel glycoproteogenomics method that allows detailed M-protein glycoprofiling by integrating patient specific Fab region sequences (genomics) with glycoprofiling by glycoproteomics. Genomic analysis uncovered a more than two-fold increase in the Fab Light Chain N-glycosylation of M-proteins of patients with Multiple Myeloma compared to healthy individuals, pointing towards an association. Subsequent glycoproteogenomics analysis of 41 patients enrolled in the IFM 2009 clinical trial revealed that the majority of the sites were fully occupied with complex type glycans, distinguishable from Fc region glycans due to high levels of sialylation, fucosylation and bisecting structures. Together, glycoproteogenomics is a powerful tool to study de novo Fab N-glycosylation in plasma cell dyscrasias and possibly other fields.
HostingRepository	PRIDE
AnnounceDate	2023-06-09
AnnouncementXML	Submission_2023-06-09_02:51:39.907.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	HansWessels
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	complex glycosylation; iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-09 05:33:32	ID requested
⏵ 1	2023-06-09 02:51:40	announced

Dataset with its publication pending

submitter keyword: glycoproteomics, glycoproteogenomics,M-protein, multiple myeloma

HansWessels
contact affiliation	Translational Metabolic Laboratory, Radboudumc, Nijmegen, The Netherlands
contact email	hans.wessels@radboudumc.nl
lab head
HansWessels
contact affiliation	Radboudumc
contact email	hans.wessels@radboudumc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD040718
     1. Label: PRIDE project
     2. Name: N-linked glycosylation of the M-protein variable region: Glycoproteogenomics reveals a new layer of personalized complexity in multiple myeloma.