ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2019
Double-Hit Gene Expression Signature Defines a Distinct Subgroup of Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma.
Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 236 papers, 1 of them a synthesis that pooled it.
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236 citing papers in PubMed, 1 synthesis or guideline pooled it, 409 citations in OpenAlex.
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- Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial.Nature medicine · 2024Trial
- Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma.The New England journal of medicine · 2022Trial
- Clinical outcomes, patterns of relapse, and molecular landscape of advanced stage high-grade B-cell lymphoma.Blood advances · 2026Article
- Diversified cell origin of Helicobacter pylori eradication-responsive gastric diffuse large B-cell lymphomas.The Journal of pathology · 2026Article
- A Patient-Derived Xenograft Repository Capturing Clinical and Molecular Heterogeneity of Large B-cell Lymphoma.Blood cancer discovery · 2026Article
- AI for prognostic assessment of diffuse large B-cell lymphoma using H&E whole-slide images.HemaSphere · 2026Article
- A phase 1 study of R-GDP-venetoclax before autologous transplant in relapsed/refractory large B-cell lymphoma (CCTG LY.18).Blood neoplasia · 2026Article
- WNK2 oncogenicity revealed by the discovery and functional characterization of novel gene isoforms in MYD88 mutated Waldenström's Macroglobulinemia.Blood cancer journal · 2026Article
- BTG1 Mutation Correlates with Inferior Prognosis in Diffuse Large B-Cell Lymphoma.Cancer research and treatment · 2026Article
- Regulatory factor X 7 limits Myc activity during B cell activation and suppresses Myc-dependent lymphomagenesis.Nature immunology · 2026Article
- A Novel CD58 Mutation-Related Signature Predicts Prognosis Risk in Diffuse Large B-Cell Lymphoma Patients.Cancer research and treatment · 2026Article
- Diffuse Large B-Cell Lymphoma: From Molecular Stratification to Precision Immunotherapy.Cells · 2026Review
- LySeqST: a targeted sequencing assay for robust genomic classification of diffuse large B-cell lymphoma.Blood advances · 2026Article
- Dose-Adjusted EPOCH-R in Aggressive B-Cell Lymphomas: Efficacy, Molecular Prognostic Factors, and Real-World Outcomes from a Multicenter Turkish Cohort-A Turkish Oncology Group (TOG) Study.Medicina (Kaunas, Lithuania) · 2026Article
- Clinicopathological and transcriptomic profiles of 101 patients with diffuse large B-cell lymphoma/high-grade B-cell lymphoma with double-hit MYC and BCL2 or BCL6 and triple hit.Histopathology · 2026Article
- Hi-C for genome-wide detection of enhancer-hijacking rearrangements in routine lymphoid cancer biopsies.Cell genomics · 2026Article
- The B-cell Receptor Blueprint in Lymphoma: Mechanisms and Therapeutic Opportunities.Blood cancer discovery · 2026Review
- Curcumin induces and enhances the PARP1-mediated parthanatos in diffuse large B cell lymphoma.Oncology letters · 2026Article
176 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeHigh-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) has a poor outcome after standard chemoimmunotherapy. We sought to understand the biologic underpinnings of HGBL-DH/TH with BCL2 rearrangements (HGBL-DH/TH- BCL2) and diffuse large B-cell lymphoma (DLBCL) morphology through examination of gene expression. PATIENTS AND
methodsWe analyzed RNA sequencing data from 157 de novo germinal center B-cell-like (GCB)-DLBCLs, including 25 with HGBL-DH/TH- BCL2, to define a gene expression signature that distinguishes HGBL-DH/TH- BCL2 from other GCB-DLBCLs. To assess the genetic, molecular, and phenotypic features associated with this signature, we analyzed targeted resequencing, whole-exome sequencing, RNA sequencing, and immunohistochemistry data.
resultsWe developed a 104-gene double-hit signature (DHITsig) that assigned 27% of GCB-DLBCLs to the DHITsig-positive group, with only one half harboring MYC and BCL2 rearrangements (HGBL-DH/TH- BCL2). DHITsig-positive patients had inferior outcomes after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone immunochemotherapy compared with DHITsig-negative patients (5-year time to progression rate, 57% and 81%, respectively; P < .001), irrespective of HGBL-DH/TH- BCL2 status. The prognostic value of DHITsig was confirmed in an independent validation cohort. DHITsig-positive tumors are biologically characterized by a putative non-light zone germinal center cell of origin and a distinct mutational landscape that comprises genes associated with chromatin modification. A new NanoString assay (DLBCL90) recapitulated the prognostic significance and RNA sequencing assignments. Validating the association with HGBL-DH/TH- BCL2, 11 of 25 DHITsig-positive-transformed follicular lymphomas were classified as HGBL-DH/TH- BCL2 compared with zero of 50 in the DHITsig-negative group. Furthermore, the DHITsig was shared with the majority of B-cell lymphomas with high-grade morphology tested.
conclusionWe have defined a clinically and biologically distinct subgroup of tumors within GCB-DLBCL characterized by a gene expression signature of HGBL-DH/TH- BCL2. This knowledge has been translated into an assay applicable to routinely available biopsy samples, which enables exploration of its utility to guide patient management.
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