Multiomic analysis identifies a high-risk signature that predicts early clinical failure in DLBCL.

Humans Lymphoma, Large B-Cell, Diffuse / genetics Male Female Gene Expression Profiling Middle Aged Transcriptome Mutation Gene Expression Regulation, Neoplastic Transcription Factors / genetics Biomarkers, Tumor / genetics Aged Prognosis Tumor Microenvironment Exome Sequencing Adult DNA-Binding Proteins / genetics Treatment Failure

Journal

Blood cancer journal

ISSN: 2044-5385

Titre abrégé: Blood Cancer J

Pays: United States

ID NLM: 101568469

Informations de publication

Date de publication:
20 Jun 2024

Historique:

received: 26 03 2024

accepted: 04 06 2024

revised: 29 05 2024

medline: 21 6 2024

pubmed: 21 6 2024

entrez: 20 6 2024

Statut: epublish

Résumé

Recent genetic and molecular classification of DLBCL has advanced our knowledge of disease biology, yet were not designed to predict early events and guide anticipatory selection of novel therapies. To address this unmet need, we used an integrative multiomic approach to identify a signature at diagnosis that will identify DLBCL at high risk of early clinical failure. Tumor biopsies from 444 newly diagnosed DLBCL were analyzed by WES and RNAseq. A combination of weighted gene correlation network analysis and differential gene expression analysis was used to identify a signature associated with high risk of early clinical failure independent of IPI and COO. Further analysis revealed the signature was associated with metabolic reprogramming and identified cases with a depleted immune microenvironment. Finally, WES data was integrated into the signature and we found that inclusion of ARID1A mutations resulted in identification of 45% of cases with an early clinical failure which was validated in external DLBCL cohorts. This novel and integrative approach is the first to identify a signature at diagnosis, in a real-world cohort of DLBCL, that identifies patients at high risk for early clinical failure and may have significant implications for design of therapeutic options.

Identifiants

DOI: 10.1038/s41408-024-01080-0 PMID: 38902256

pubmed: 38902256

doi: 10.1038/s41408-024-01080-0

pii: 10.1038/s41408-024-01080-0

doi:

Substances chimiques

Transcription Factors 0

Biomarkers, Tumor 0

DNA-Binding Proteins 0

ARID1A protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

100

Subventions

Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)

ID : SPORE-P50 CA97274

Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)

ID : R01 CA212162-01A1

Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)

ID : CA195568

Informations de copyright

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