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Omics · study · 2026

Pathogenesis of Diffuse Large B-cell Lymphoma Proteogenotypes

Listed in NCBI GEO

The clinical and molecular heterogeneity of diffuse large B-cell lymphoma (DLBCL) is incompletely understood.

Description

By integrating proteomic, transcriptomic and genomic data from 478 DLBCL tumors, we identify seven DLBCL proteogenotypes (PGs) reflecting specific pathophysiological features and spanning cell-of-origin (COO) as well as genetic subtypes. PG4 is associated with poor outcome, independent of known risk factors including COO, genetic features or the international prognostic index.

PG4 is enriched for subsets of activated B-cell-like DLBCL, germinal-center-B-cell-like tumors and genetically unclassified cases. It shares a dark-zone related B-cell phenotype and an enrichment of BTG1 and TBL1XR1 mutations. Single-cell sequencing and spatial transcriptomics further reveals enhanced MYC and TCF3/4 transcriptional activity while MYC translocations were absent, as well as exhausted CD8 T cells as common driver mechanisms in PG4.

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Our proteogenomic framework identifies heretofore unknown biological heterogeneity among DLBCL tumors, including high-risk proteogenomic features that provide a basis for innovative diagnostic and therapeutic approaches.

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Life Sciences
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Biochemistry and cell biology 72% · Genome sequencing 65% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE32497710 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[field].anzsrc:group:3101enrichment · NCBI GEOtaxonomy-embedding@1.1.0title+keywords+description (72%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:genome-sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title