PXD038437-2

PXD038437 is an original dataset announced via ProteomeXchange.

Title	Proteogenomic landscape of multiple myeloma
Description	Multiple myeloma is a plasma cell malignancy of the bone marrow. Despite therapeutic advances, multiple myeloma remains incurable and better risk stratification as well as new therapies are therefore highly needed. The proteome of multiple myeloma has not been systematically assessed before and holds the potential to uncover additional insight into disease biology and improved prognostic models. Here, we provide a comprehensive multi-omics analysis including deep tandem mass tags (TMT)-based quantitative global (phospho)proteomics, RNA sequencing and nanopore DNA sequencing of 138 primary patient-derived plasma cell malignancies encompassing treatment-naive multiple myeloma patients treated in clinical trials, plasma cell leukemia, and the premalignancy monoclonal gammopathy of undetermined significance (MGUS), as well as healthy controls. We found that the (phospho)proteome of malignant plasma cells is highly deregulated as compared to healthy plasma cells and is both defined by chromosomal alterations and extensive post-transcriptional regulation. A protein signature was identified that is associated with aggressive disease and more predictive for outcome than cytogenetic-based risk assessment in newly diagnosed multiple myeloma. Integration with functional genetics and single-cell sequencing revealed generally and genetic subtype-specific deregulated proteins and pathways in plasma cell malignancies that include novel potential targets for (immuno)therapies. These findings provide new insights in the biology of multiple myeloma and will be a unique resource for investigating new therapeutic approaches.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:49:38.974.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Evelyn Ramberger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-27 00:08:39	ID requested
1	2024-07-12 08:36:13	announced
⏵ 2	2024-10-22 06:49:39	announced	2024-10-22: Updated project metadata.

10.1038/s43018-024-00784-3;

Ramberger E, Sapozhnikova V, Ng YLD, Dolnik A, Ziehm M, Popp O, Str, ä, ng E, Kull M, Gr, ü, nschl, ä, ger F, Kr, ü, ger J, Benary M, M, ü, ller S, Gao X, Murgai A, Haji M, Schmidt A, Lutz R, Nogai A, Braune J, Laue D, Langer C, Khandanpour C, Bassermann F, D, ö, hner H, Engelhardt M, Straka C, Hundemer M, Beule D, Haas S, Keller U, Einsele H, Bullinger L, Knop S, Mertins P, Kr, ö, nke J, The proteogenomic landscape of multiple myeloma reveals insights into disease biology and therapeutic opportunities. Nat Cancer, 5(8):1267-1284(2024) [pubmed]

submitter keyword: multiple myeloma, proteogenomics, plasma cells, therapeutic targets, clinical proteomics, risk signatures, biomarkers

Philipp Mertins
contact affiliation	Proteomics Platform, Max Delbrück Center for Molecular Medicine, Berlin, Germany
contact email	Philipp.Mertins@mdc-berlin.de
lab head
Evelyn Ramberger
contact affiliation	Max Delbrück Center for Molecular Medicine, Berlin
contact email	evelyn.ramberger@mdc-berlin.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038437
     1. Label: PRIDE project
     2. Name: Proteogenomic landscape of multiple myeloma