Our results suggest that an integrated NGS strategy should not replace FISH or be routinely used in the workup to detect the clinically relevant rearrangements in HGBCL. It may serve as a complement to FISH testing when FISH shows negative results.

4 days ago

Clinical • Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)

MYC rearrangement + BCL2 rearrangement • MYC rearrangement • BCL6 rearrangement • BCL2 rearrangement • BCL6 fusion

11ms

Non-IG::MYC in diffuse large B-cell lymphoma confers variable genomic configurations and MYC transactivation potential. (PubMed, Leukemia)

Translocation breakpoint analyses of 8 cases by TLC-based NGS showed no obvious genomic configuration that enables MYC transactivation in 3 of the 4 cases with non-IG::MYC, while a typical promoter substitution or IGH super enhancer juxtaposition in the remaining cases. The findings potentially explain variable MYC expression in DLBCL with MYC translocation, and also bear practical implications in its routine assessment.

11 months ago

Journal • IO biomarker

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)

MYC expression • MYC translocation • BCL6 translocation • BCL6 fusion

1year

Deciphering the Clinical Benefit of Pola-R-CHP versus R-CHOP in Different Genetic Subtypes Beyond Cell of Origin in the POLARIX Study (ASH 2023)

Introduction: In the POLARIX study, polatuzumab vedotin in combination with rituximab plus cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) demonstrated prolonged progression-free survival (PFS) vs rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients (pts) with previously untreated diffuse large B-cell lymphoma (DLBCL; NCT03274492; Tilly et al. In this exploratory biomarker analysis, we recapitulated that pts with molecularly defined DLBCL subtypes, including EZB and MCD by LymphGen and DZsig+ by RNAseq, have poor outcomes with R-CHOP therapy. In pts with the EZB and MCD subtypes, Pola-R-CHP appeared to improve 2-year PFS compared with R-CHOP. Pts with GCB DLBCL who were DZsig+ significantly benefited from Pola-R-CHP vs R-CHOP.

1 year ago

Clinical • IO biomarker

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • CD79B (CD79b Molecule) • NOTCH2 (Notch 2)

EZH2 mutation • CD79B mutation • CD79B mutation • MYC translocation • NOTCH2 mutation • BCL6 translocation • BCL6 fusion + NOTCH2 mutation • BCL2 translocation • BCL6 fusion

Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • vincristine • prednisone • Polivy (polatuzumab vedotin-piiq)

1year

Clinicopathologic and mutational profiles of primary breast diffuse large B cell lymphoma in a male patient: case report and literature review. (PubMed, World J Surg Oncol)

We reported a relatively rare PB-DLBCL in a male, non-GBC phenotype, dual-expression type. It is worth mentioning that this case had IgH/BCL6 fusion, nonsense mutations in TNFAIP3, frameshift mutations in PRDM1, and missense mutations in CREBBP, DTX1, and FOXO1. To the best of our knowledge, this case is the first report of genomic mutational profiles of PB-DLBCL in males.

1 year ago

Review • Journal • IO biomarker

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • BCL6 (B-cell CLL/lymphoma 6) • CREBBP (CREB binding protein) • TNFAIP3 (TNF Alpha Induced Protein 3) • IRF4 (Interferon regulatory factor 4) • MME (Membrane Metalloendopeptidase) • PRDM1 (PR/SET Domain 1)

CD20 positive • BCL2 positive • CREBBP mutation • MYC rearrangement • BCL6 rearrangement • BCL2 rearrangement • PRDM1 mutation • BCL6 positive • BCL6 fusion

Rituxan (rituximab) • cytarabine • Yinuokai (orelabrutinib)

over1year

Chromosomal Aberration t(14;17)(q32;q21) Simultaneously Activates HOXB5 and miR10a in Triple-Hit B-Cell Lymphoma. (PubMed, Biomedicines)

Functional investigations showed that HOXB5 represses the apoptotic driver BCL2L11 and promotes survival in the presence of etoposide, and that miR10a inhibits BCL6 and may thus play an oncogenic role in later stages of lymphomagenesis. Collectively, we characterize triple-hit B-cell line SC-1 and identify the aberrant expression of HOXB5 and miR10a, both novel oncogenes in B-cell lymphoma.

over 1 year ago

Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • BCL2L11 (BCL2 Like 11) • ZNF501 (Zinc Finger Protein 501)

MYC rearrangement • BCL2 rearrangement • BCL6 fusion

etoposide IV

over1year

Simplified algorithm for genetic subtyping in diffuse large B-cell lymphoma. (PubMed, Signal Transduct Target Ther)

Genetic subtype-guided targeted agents achieved encouraging clinical response when combined with immunochemotherapy. Collectively, LymphPlex provided high efficacy and feasibility, representing a step forward to the mechanism-based targeted therapy in DLBCL.

over 1 year ago

Journal • IO biomarker

TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • ARID1A (AT-rich interaction domain 1A) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • B2M (Beta-2-microglobulin) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CD70 (CD70 Molecule) • EP300 (E1A binding protein p300) • TNFAIP3 (TNF Alpha Induced Protein 3) • GNA13 (G Protein Subunit Alpha 13) • IRF8 (Interferon Regulatory Factor 8) • PIM1 (Pim-1 Proto-Oncogene) • TNFRSF14 (TNF Receptor Superfamily Member 14) • CCND3 (Cyclin D3) • IRF4 (Interferon regulatory factor 4) • SOCS1 (Suppressor Of Cytokine Signaling 1) • PRDM1 (PR/SET Domain 1) • STAT6 (Signal transducer and activator of transcription 6) • TNFRSF18 (TNF Receptor Superfamily Member 18) • BTG2 (BTG Anti-Proliferation Factor 2) • DDX3X (DEAD-Box Helicase 3 X-Linked) • TBL1XR1 (TBL1X Receptor 1) • ZFP36 (ZFP36 Ring Finger Protein)

TP53 mutation • ARID1A mutation • NOTCH1 mutation • EZH2 mutation • MYC expression • MYC rearrangement • STAT3 mutation • GNA13 mutation • PRDM1 mutation • IRF8 mutation • BCL2 fusion • BCL6 fusion

2years

EZH2 inhibitor DZNep blocks cell proliferation of GCB-DLBCL cells by upregulating p16. (PubMed, Leuk Lymphoma)

These results suggest that DZNep may have potential as a novel therapeutic agent for DFLBL therapy. This agent may serve as a novel molecular agent to be applied to GCB DLBCL.

2 years ago

Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • CD79B (CD79b Molecule) • NOTCH2 (Notch 2)

NOTCH1 mutation • EZH2 mutation • MYD88 L265P • NOTCH2 mutation • BCL2 fusion • BCL6 fusion

almost3years

Comparison Between Integrated Genomic DNA/RNA Profiling and Fluorescence In Situ Hybridization in the Detection of MYC, BCL-2, and BCL-6 Gene Rearrangements in Large B-Cell Lymphomas: An Update (USCAP 2022)

CGP appears more sensitive than FISH in detection of IGH-BCL2 and IGH-MYC rearrangements. FISH testing is superior for detection of non-IGH-MYC. Neither FISH nor CGP detect all DHLs.

almost 3 years ago

IO biomarker

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)

MYC rearrangement + BCL2 rearrangement • MYC rearrangement • BCL2 rearrangement • BCL6 fusion

3years

Molecular Characterization of Diffuse Large B-Cell Lymphoma Associated to Hepatitis C Virus Infection (ASH 2021)

Twenty-seven pts (50%) received rituximab-enriched protocols, 23 pts (43%) were treated with chemotherapy alone, 1 pt (2%) with surgery alone, 3 pts (5%) were lost to follow up...The prevalence of the BN2 cluster and enrichment of mutations of genes involved in NOTCH pathway seem to indicate a preferential marginal-zone origin in HCV-positive DLBCL. In addition, our data confirm the absence of BCL2 translocation in this subset of DLBCL and show a high prevalence of mutated genes within the epigenetic and immune regulation pathways in HCV-positive DLBCL, pointing out their compelling role in the pathogenesis and suggesting potential implications for molecularly targeted therapies.

3 years ago

Tumor Mutational Burden • IO biomarker

TMB (Tumor Mutational Burden) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • KMT2D (Lysine Methyltransferase 2D)

LDH elevation • KMT2D mutation • MYC translocation • BCL2 translocation • BCL6 fusion

Rituxan (rituximab)