Diffuse Large B-Cell Lymphoma NOS (DLBCLNOS)

Overview

Diffuse large B-cell lymphoma, not otherwise specified — the parent OncoTree category encompassing PCNSL and secondary CNS DLBCL variants.

Cohorts in the corpus

Recurrent alterations

  • BCR-pathway drivers dominate the CNS DLBCL subset: MYD88, CD79B, CARD11, and TBL1XR1 PMID:38995739.
  • LymphGen molecular subclassification on a 400-gene targeted NGS panel (MSK-IMPACT Heme) achieves 92% overall accuracy (86% sensitivity, 98% specificity) in 396 DLBCL cases; 55% classified into 6 subtypes (MCD 10%, EZB 22%, BN2 10%, N1 3%, ST2 7%, A53 2%) PMID:38497151.
  • BCL2 translocation enriched in EZB subtype (81%); BCL6 translocation enriched in BN2 subtype (77%); TP53 mutations/CNA define A53 subtype PMID:38497151.
  • Exome sequencing of DLBCL tumors identified frequent somatic mutations in histone-modifying genes MLL2, MEF2B, EZH2, and CREBBP, with MLL2 mutated in ~32% of cases PMID:21796119
  • WES of 55 diffuse large B-cell lymphoma tumors identified recurrent mutations; MutSig analysis revealed significantly mutated genes including those in BCR and TLR signaling PMID:22343534
  • PCNSL is a CNS-restricted subtype of DLBCLNOS; genomic profiling of 19 immunocompetent PCNSL cases identified PCNSL-specific biallelic inactivation of TOX and PRKCD, and BCR/TLR/NF-κB pathway alterations in >90% of cases, shared with systemic DLBCL but with higher MYD88 mutation prevalence (~79%) PMID:25991819
  • Integrative WES + RNA-seq of 1001 de novo DLBCL patients (Reddy et al.) identified 150 recurrent driver genes, defined ABC/GCB subtype-specific essentialities by genome-wide CRISPR screen, and built a multivariate genomic risk model (IPI + cell-of-origin + MYC/BCL2 + driver-gene mutations) that outperformed standard prognostic tools across complete-responder and IPI-stratified subgroups PMID:28985567
  • Pan-cancer fusion study (9,624 TCGA samples) included DLBCL (TCGA cohort identifier mapping to DLBCLNOS) as one of 33 cancer types; druggable fusions were annotated across 29 cancer types PMID:29617662

Subtypes

  • PCNSL — primary CNS lymphoma, predominantly non-germinal-center PMID:38995739.
  • Secondary CNS lymphoma (SCNSL) — systemic DLBCL with CNS involvement; 15 patients in the MSK ibrutinib cohort with 60% ORR (7 CR) PMID:38995739.

Therapeutic landscape

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:21796119

This page was processed by crosslinker on 2026-05-14. - PMID:22343534

This page was processed by crosslinker on 2026-05-14. - PMID:25991819

This page was processed by crosslinker on 2026-05-14. - PMID:28985567

This page was processed by wiki-cli on 2026-05-15. - PMID:29617662

This page was processed by wiki-cli on 2026-05-15.