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BIOMARKER:

NOTCH2 mutation

i
Entrez ID:
Related biomarkers:
8d
TP53 Mutation Is the Only Robust Mutational Biomarker for Outcome Found in a Consecutive Clinical Cohort of Real-Word Patients With Primary Large B-Cell Lymphoma. (PubMed, Eur J Haematol)
With a targeted gene panel and NGS methodology feasible in daily diagnostic routine, we identified high-risk gene mutations with a significant prognostic impact of which TP53 mutations were reproducible across validation cohorts.
Journal
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TP53 (Tumor protein P53) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD79B (CD79b Molecule) • NOTCH2 (Notch 2) • PRDM1 (PR/SET Domain 1)
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TP53 mutation • NOTCH2 mutation
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Rituxan (rituximab)
9ms
Notch signaling genes and CD8+ T-cell dynamics: Their contribution to immune-checkpoint inhibitor therapy in oral squamous cell carcinoma: A retrospective study. (PubMed, Cancer Med)
Four of 10 patients were positive for PD-L1 and CD8+ T. By analyzing WES in three of these four patients, we notably identified the mutations of NOTCH1, FBXW7, and noncoding RNA intronic mutation in NOTCH2NLR in two of these three patients. This study may enable better selection of ICI therapy with CD8+ T-cell infiltration via PD-L1 expression for oral squamous cell carcinoma patients with mutations in Notch signaling pathway.
Retrospective data • Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • NOTCH1 (Notch 1) • CD8 (cluster of differentiation 8) • FBXW7 (F-Box And WD Repeat Domain Containing 7)
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PD-L1 expression • NOTCH1 mutation • NOTCH2 mutation • NOTCH mutation
1year
Dedifferentiated Leiomyosarcoma-morphology, Immunohistochemistry, and Molecular Findings of a Case and Review of Literature. (PubMed, Int J Gynecol Pathol)
The patient was subsequently treated with 6 cycles of adriamycin chemotherapy. Computerized tomography scan after 3 cycles showed no residual disease. Published literature regarding dedifferentiated leiomyosarcoma is reviewed.
Review • Journal
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TP53 (Tumor protein P53) • NF1 (Neurofibromin 1) • NOTCH2 (Notch 2)
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TP53 mutation • NF1 mutation • NOTCH2 mutation
|
doxorubicin hydrochloride
1year
The Proliferative History Index, Epicmit, Derived from Genome-Wide Epigenomic Profiling, Is a Key Driver of Clinical Survival in Splenic Marginal Zone Lymphoma (ASH 2023)
We then conducted univariate Cox Proportional Hazards analysis to investigate the prognostic significance of clinical and molecular features on time to first treatment (TTFT; most prevalent treatments: splenectomy, n=51; rituximab, n=20) and overall survival (OS)...To conclude, we demonstrate the potential clinical utility of epiCMIT score in SMZL patients, identifying that SMZL patients with high epiCMIT harbour specific genetic characteristics, and exhibit reduced treatment-free survival. EpiCMIT could be valuable in clinical practice, helping to identify those patients destined to progress and require closer monitoring.
Clinical • Tumor mutational burden
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • BCOR (BCL6 Corepressor) • CARD11 (Caspase Recruitment Domain Family Member 11) • MIR155 (MicroRNA 155) • NFKB1 (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1)
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TP53 mutation • NOTCH2 mutation • Chr del(7q)
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Rituxan (rituximab)
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.
Clinical • IO biomarker
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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)
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EZH2 mutation • CD79B mutation • CD79B mutation • MYC translocation • NOTCH2 mutation • BCL6 translocation • BCL6 fusion + NOTCH2 mutation • BCL2 translocation • BCL6 fusion
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Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • vincristine • prednisone • Polivy (polatuzumab vedotin-piiq)
1year
Plasma Circulating Tumor DNA (ctDNA) as an Alternative to Tissue DNA for Genotyping of DLBCL: Results from the POLARIX Study (ASH 2023)
Introduction: In the POLARIX study (NCT03274492), polatuzumab vedotin in combination with rituximab plus cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) demonstrated prolonged progression-free survival (PFS) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated diffuse large B-cell lymphoma (DLBCL; Tilly et al. Our analyses demonstrated that the mutation landscape of ctDNA in DLBCL characterized by the AVENIO ctDNA NHL assay resembles that of tumor tissue determined by WES. Patients with molecular subtypes defined by WES or ctDNA had similar PFS outcomes. Overall, these findings support the use of plasma ctDNA as an alternative to tumor tissue for the genotyping of DLBCL.
IO biomarker • Circulating tumor DNA
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TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • NOTCH1 (Notch 1) • BCL6 (B-cell CLL/lymphoma 6) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • NOTCH2 (Notch 2) • TNFAIP3 (TNF Alpha Induced Protein 3) • DCHS1 (Dachsous Cadherin-Related 1) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
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TP53 mutation • NOTCH1 mutation • TET2 mutation • KMT2D mutation • EZH2 mutation • MYD88 L265P • CD79B mutation • BCL6 rearrangement • CD79B mutation • NOTCH2 mutation • BCL2 rearrangement • BCL6 translocation • MYD88 L265P + CD79B mutation • TP53BP1 mutation • BCL2 translocation
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Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • vincristine • prednisone • Polivy (polatuzumab vedotin-piiq)
1year
DNA Methylation-Based Classification of Hairy Cell Leukemia and Splenic B Cell Lymphoma (ASH 2023)
In summary, we have developed a DNA methylation-based classifier that resolves 4 SBLPN subgroups with distinct molecular features, and reclassifies a subset of SMZL and HCL patients, adding further information to the updated WHO/ICC entities. We reveal distinct biological pathways operating in M-SBLPN subgroups that may aid targeted therapy approaches.
Epigenetic controller
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BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • TERT (Telomerase Reverse Transcriptase) • IGH (Immunoglobulin Heavy Locus) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein) • BIRC3 (Baculoviral IAP repeat containing 3) • IL2RA (Interleukin 2 receptor, alpha) • SYK (Spleen tyrosine kinase) • IGLL5 (Immunoglobulin Lambda Like Polypeptide 5)
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TP53 mutation • BRAF V600E • BRAF V600 • BIRC3 mutation • TERT mutation • NOTCH2 mutation • TERT promoter mutation • SYK mutation • TERT 124C>T
over1year
Skin Glomus Tumors: A Pathologic and Molecular Study of 11 Cases (ASDP 2023)
Skin primary glomus tumors show frequent mutations in NOTCH2 and NOTCH3 , including gene fusions and novel truncating mutations. The presence of occasional BRAF and PDGFRB alterations raise the possibility of targeted therapies in clinically-advanced cases of this tumor type.
Clinical • Tumor mutational burden
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BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ATRX (ATRX Chromatin Remodeler) • NOTCH2 (Notch 2) • NOTCH3 (Notch Receptor 3)
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BRAF V600E • BRAF V600 • ATRX mutation • NOTCH2 mutation • NOTCH3 mutation • PDGFRB mutation
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FoundationOne® CDx
over1year
NOTCH2 gene mutation and gamma-secretase inhibitor in mediating the malignancy of ovarian cancer. (PubMed, Aging (Albany NY))
Furthermore, the NOTCH2-mediated tumorigenesis was mostly reversed after NF-κB inhibitor Bay11-7082 treatment. These findings identified the NOTCH2 P2113S mutation in ovarian carcinogenesis, and NOTCH2 P2113S is a potential target in treating OC.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • NOTCH2 (Notch 2) • BAX (BCL2-associated X protein) • HES1 (Hes Family BHLH Transcription Factor 1)
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NOTCH2 mutation • NOTCH mutation
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Bay11-7082
over1year
Mutations Detected in Real World Clinical Sequencing during BTK Inhibitor Treatment in Chronic Lymphocytic Leukemia (CLL) (IWCLL 2023)
73 patients had only one BTKi (ibrutinib (IBR), 64; acalabrutinib (ACA), 9). 12 pts had multiple BTKis, 8 with two drugs with IBR first followed by ACA (Nf3, 37.5%), vecabrutinib (Nf1, 12.5%), and PIR (Nf4, 50.0%); and 4 with three or more drugs... Our retrospective report summarizes mutations detected during BTKi treatment and shows that BTK L528W can occur during both covalent and non-covalent BTK inhibitor therapy. Four of six patients who progressed on PIR had T474 mutations. In addition, our results may suggest that activating mutations in RAS/RAF/MAPK pathway are related to BTKi resistance.
Clinical • Real-world evidence • IO biomarker • Real-world
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • SF3B1 (Splicing Factor 3b Subunit 1) • NOTCH2 (Notch 2) • PLCG2 (Phospholipase C Gamma 2) • XPO1 (Exportin 1)
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TP53 mutation • KRAS mutation • BRAF mutation • NRAS mutation • Chr del(11q) • RAS mutation • SF3B1 mutation • BTK C481S • NOTCH2 mutation • PLCG2 mutation • BTK mutation • BTK C481R • BTK C481Y • BTK R665W • BTK T474I • BTK L845F • PLCG2 L845F • XPO1 mutation
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Imbruvica (ibrutinib) • Calquence (acalabrutinib) • vecabrutinib (SNS-062)
over1year
Integrated clinical genomic analysis reveals xenobiotic metabolic genes are downregulated in meningiomas of current smokers. (PubMed, J Neurooncol)
In this study, we conducted a comparative analysis of meningioma patients based on their smoking history, examining both their clinical trajectories and molecular changes. Meningiomas from current smokers were more likely to harbor NOTCH2 mutations, and AKT1 mutations were absent in current or past smokers. Moreover, both current and past smokers exhibited a mutational signature associated with DNA mismatch repair. Meningiomas from current smokers demonstrate downregulation of xenobiotic metabolic enzymes UGT2A1 and UGT2A2, which are downregulated in other smoking related cancers. Furthermore, current smokers exhibited downregulation xenobiotic metabolic gene sets, as well as enrichment in gene sets related to mitotic spindle, E2F targets, and G2M checkpoint, which are hallmark pathways involved in cell division and DNA replication control. In aggregate, our results demonstrate novel alterations in meningioma molecular biology in response to systemic carcinogens.
Journal • Tumor mutational burden
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TMB (Tumor Mutational Burden) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • NOTCH2 (Notch 2) • UGT2A1 (UDP Glucuronosyltransferase Family 2 Member A1 Complex Locus) • UGT2A2 (UDP Glucuronosyltransferase Family 2 Member A2)
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AKT1 mutation • NOTCH2 mutation
over1year
DLBCL associated NOTCH2 mutations escape ubiquitin-dependent degradation and promote chemo-resistance. (PubMed, Blood)
Up to 40% of DLBCL patients display refractory disease or relapse after standard chemotherapy treatment (R-CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), leading to significant morbidity and mortality. Targeting CHOP-resistant DLBCL tumors with the Phase 3 clinical trial molecules nirogacestat, a selective g-secretase inhibitor, and ipatasertib, a pan-AKT inhibitor, synergistically promotes DLBCL death. These findings establish the rationale for therapeutic strategies aimed at targeting the oncogenic pathway activated in KLHL6- or NOTCH2-mutated DLBCL.
Journal
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NOTCH2 (Notch 2) • KLHL6 (Kelch Like Family Member 6)
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NOTCH2 mutation
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Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • ipatasertib (RG7440) • vincristine • prednisone • Ogsiveo (nirogacestat)
over1year
Genetic and Pathway Alterations of Prostate Cancer : From Localized to Metastatic Prostate Cancer (AUA 2023)
Through genetic analysis of prostate cancer, it was possible to analyze numerous gene mutations, and to find clinically significant mutations. Several genes, such as BRCA2, NOTCH2 and TP53 gene mutations have been found to be associated with advanced prostate cancer. The prognosis of prostate cancer can be predicted by genetic analysis, and the better prognosis can be expected through the application of a proper targeted therapy for each pathway alterations.
BRCA Biomarker • Metastases
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • KMT2C (Lysine Methyltransferase 2C) • NOTCH2 (Notch 2) • SPOP (Speckle Type BTB/POZ Protein)
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TP53 mutation • BRCA2 mutation • BRCA1 mutation • PIK3CA mutation • PTEN mutation • NOTCH2 mutation
almost2years
Pre-clinical efficacy of targeting BAF complexes through inhibition of the dual ATPases BRG1 and BRM by FHD-286 in cellular models of AML (AACR 2023)
Additionally, co-treatment with FHD-286 and venetoclax, decitabine or OTX015, as compared to each drug alone or vehicle control, significantly reduced AML burden and improved the overall survival of the NSG mice, without inducing significant toxicity. Taken together, these findings highlight the promise of FHD-286 treatment alone and in rational combinations in exerting significant anti-AML efficacy against cellular models of AML, especially those with MLL-r, mtNPM1 or chromosome 3q26 lesions and EVI1 overexpression.
Preclinical • IO biomarker
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FLT3 (Fms-related tyrosine kinase 3) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDK4 (Cyclin-dependent kinase 4) • KMT2C (Lysine Methyltransferase 2C) • NOTCH2 (Notch 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CDK6 (Cyclin-dependent kinase 6) • SPI1 (Spi-1 Proto-Oncogene) • MEF2C (Myocyte Enhancer Factor 2C) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
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NPM1 mutation • MLL rearrangement • MLL rearrangement • BCL2 expression • MYC expression • NOTCH2 mutation • KMT2A expression
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Venclexta (venetoclax) • decitabine • birabresib (OTX015) • FHD-286
almost2years
Journal • Next-generation sequencing • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein) • CD5 (CD5 Molecule) • TNFRSF14 (TNF Receptor Superfamily Member 14) • STAT6 (Signal transducer and activator of transcription 6) • TNFRSF18 (TNF Receptor Superfamily Member 18)
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EZH2 mutation • CREBBP mutation • BCL6 rearrangement • NOTCH2 mutation • BCL2 rearrangement
2years
Zanubrutinib plus salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma. (PubMed, Front Immunol)
With high efficacy and manageable tolerability, zanubrutinib plus salvage chemotherapy may be a potential treatment option for R/R DLBCL. CAR-T cell therapy may be a priority strategy for these poor responders to BTKi-based treatment.
Retrospective data • Journal • IO biomarker
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TP53 (Tumor protein P53) • CD19 (CD19 Molecule) • NOTCH2 (Notch 2)
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TP53 mutation • NOTCH2 mutation
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Brukinsa (zanubrutinib)
2years
Establishment and characterization of a new mantle cell lymphoma cell line with a NOTCH2 mutation, Arbo. (PubMed, EJHaem)
Arbo represents a NOTCH2 mutated model that is useful in MCL as well as other lymphomas with such mutation. We plan to deposit Arbo at the ATCC to be available for the research community.
Preclinical • Journal
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NOTCH2 (Notch 2) • FCER2 (Fc Fragment Of IgE Receptor II)
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NOTCH2 mutation
2years
Pre-Clinical Efficacy of Targeting Baf Complexes through Inhibition of the Dual Atpases BRG1 and BRM By FHD-286 in Cellular Models of AML of Diverse Genetic Background (ASH 2022)
Based on these observations, and clinical efficacy of the combination of venetoclax and decitabine/azacitidine, we determined the in vitro lethal activity of co-treatment with FHD-286 and venetoclax or decitabine against AML cell lines and PD AML cells. Additionally, co-treatment with FHD-286 and venetoclax or decitabine or OTX015, as compared to each drug alone or vehicle control, significantly reduced the AML burden and improved median and overall survival of the immune-depleted mice, without inducing significant toxicity. Taken together, these findings highlight the promise of FHD-286 treatment alone and in rational combinations in exerting significant anti-AML efficacy against cellular models of AML, especially those with MLL-r, mtNPM1 or chromosome 3q26 lesions and EVI1 overexpression.
Preclinical • IO biomarker
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FLT3 (Fms-related tyrosine kinase 3) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • KMT2C (Lysine Methyltransferase 2C) • NOTCH2 (Notch 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • ITGAM (Integrin, alpha M) • SPI1 (Spi-1 Proto-Oncogene) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
|
BCL2 expression • MYC expression • NOTCH2 mutation • KMT2A expression • ITGAM expression
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Venclexta (venetoclax) • azacitidine • decitabine • birabresib (OTX015) • FHD-286
2years
Towards a Unified Genetic Classification System for Diffuse Large B-Cell Lymphoma (DLBCL) (ASH 2022)
We present here a refined classification of DLBCL genetic subgroups that combines previously described classification algorithms and extends it to allow classification of more tumors into additional subgroups that preserve the major divisions of existing systems. This represents an important advancement that will facilitate further understanding of genomic complexity in this disease.
IO biomarker
|
TP53 (Tumor protein P53) • 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) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein) • PAX5 (Paired Box 5) • PIM1 (Pim-1 Proto-Oncogene) • TNFRSF14 (TNF Receptor Superfamily Member 14) • IRF4 (Interferon regulatory factor 4) • STAT6 (Signal transducer and activator of transcription 6) • TNFRSF18 (TNF Receptor Superfamily Member 18)
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TP53 mutation • MYC rearrangement • MYC translocation • NOTCH2 mutation • PIM1 mutation • TNFRSF14 mutation
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.
Journal • IO biomarker
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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)
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NOTCH1 mutation • EZH2 mutation • MYD88 L265P • NOTCH2 mutation • BCL2 fusion • BCL6 fusion
2years
Intravascular Large B-Cell Lymphoma Genomic Profile Is Characterized by Alterations in Genes Regulating NF-κB and Immune Checkpoints. (PubMed, Am J Surg Pathol)
Our results confirm the relevance of mutations in B-cell receptor/nuclear factor-κB signaling and immune escape pathways in IVLBCL and identify novel driver alterations. The similar mutational profile in tumors with extravascular dissemination suggests that these cases may also be considered in the spectrum of IVLBCL.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • ETV6 (ETS Variant Transcription Factor 6) • CD79B (CD79b Molecule) • NOTCH2 (Notch 2) • GNA13 (G Protein Subunit Alpha 13) • PIM1 (Pim-1 Proto-Oncogene) • CCND3 (Cyclin D3) • IRF4 (Interferon regulatory factor 4) • BTG2 (BTG Anti-Proliferation Factor 2)
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PD-L1 expression • MYD88 L265P • CD79B mutation • CD79B mutation • NOTCH2 mutation • PIM1 mutation • MYD88 L265P + CD79B mutation
over2years
Clear cell variant of atypical fibroxanthoma and pleomorphic dermal sarcoma: molecular characterisation of two cases (ECP 2022)
Clear cell AFX and PDS seem to share fundamental molecular driver events. Their molecular profle is also similar to that described in more common variants. Whilst no unique mutational profle was identi-fed in our cases, presence of the genetic abnormalities described herein may increase the level of confdence in diagnosing these lesions.
Clinical • Tumor mutational burden
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • TERT (Telomerase Reverse Transcriptase) • APC (APC Regulator Of WNT Signaling Pathway) • NOTCH2 (Notch 2) • MME (Membrane Metalloendopeptidase)
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TP53 mutation • TMB-H • CDKN2A mutation • APC mutation • NOTCH2 mutation
|
TruSight Oncology 500 Assay
over2years
Myeloid Nuclear Differentiation Antigen (MNDA): an aid in differentiating lymphoplasmayctic lymphoma and splenic marginal zone lymphoma in bone marrow biopsies at presentation. (PubMed, Hum Pathol)
On the widest case-series so far published focusing on LPL and SMZL immunohistochemical diagnosis at onset on BMB, we demonstrated that MNDA expression significantly support the diagnosis of SMZL. This observation may be of particular help in cases where the MYD88 p.Leu265Pro mutational status and/or SMZL-related genetic aberrations are unavailable.
Journal
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MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • NOTCH2 (Notch 2) • FCER2 (Fc Fragment Of IgE Receptor II)
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MYD88 mutation • MYD88 L265P • NOTCH2 mutation
over2years
CLINICAL APPLICABILITY OF TARGETED NEXT-GENERATION SEQUENCING FOR PRECISION MEDICINE IN DIFFUSE LARGE B CELL LYMPHOMA (EHA 2022)
Ibrutinib, as a single agent, has demonstrated limited activity in DLBCL with mutant MYD88 and wildtype CD79 . In this study, we identified 3 patients with mutant MYD88 and wildtype CD79A/B (8.1%), among whom 2 harbored MYD88 L265P variants and 1 had MYD88 S219C mutation. Conclusion The utility of mutational profiling may facilitate the identification of potential drug targets, which in turns may represent new therapeutic possibilities.
Clinical • Next-generation sequencing
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • DNMT3A (DNA methyltransferase 1) • ARID1A (AT-rich interaction domain 1A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2D (Lysine Methyltransferase 2D) • LRP1B (LDL Receptor Related Protein 1B) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • CARD11 (Caspase Recruitment Domain Family Member 11) • EP300 (E1A binding protein p300) • CD79A (CD79a Molecule) • IRF4 (Interferon regulatory factor 4) • TYK2 (Tyrosine Kinase 2)
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TP53 mutation • ARID1A mutation • RUNX1 mutation • MYD88 mutation • LRP1B mutation • MYD88 L265P • LDH-L • NOTCH2 mutation • MYD88 wild-type • LDH-H
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Imbruvica (ibrutinib)
almost3years
Establishment and characterization of a new mantle cell lymphoma cell line with a NOTCH2 mutation, ArBo (AACR 2022)
Additionally, a dose dependent decrease in the expression of CD23 was observed by flow cytometry following treatment with gliotoxin.To determine the dependence of Arbo on B-cell receptor (BCR) signaling for survival, we cultured the cells with increasing concentrations of the BTK inhibitor ibrutinib for 48h. Inhibition of cell growth was observed in a dose-dependent manner resulting in an IC50 of 0.4 µM.In conclusion, Arbo is a novel blastoid MCL cell line with a NOTCH2 mutation that is fully characterized and will be made available to the research community.Supported by a grant from the Ladies Leukemia League, Inc., of the Gulf South Region.
Preclinical • IO biomarker
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TP53 (Tumor protein P53) • CCND1 (Cyclin D1) • CD38 (CD38 Molecule) • NOTCH2 (Notch 2) • CD5 (CD5 Molecule) • FCER2 (Fc Fragment Of IgE Receptor II)
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TP53 mutation • ATM mutation • Chr t(11;14) • Chr t(11;14)(q13;q32) • NOTCH2 mutation • CD5 positive
|
Imbruvica (ibrutinib)
almost3years
Plasticity in the Absence of NOTCH Uncovers a RUNX2-Dependent Pathway in Small Cell Lung Cancer. (PubMed, Cancer Res)
Notch2-mutant non-neuroendocrine cells highly express innate immune signaling genes including STING and were sensitive to STING agonists. This work identifies a Notch-independent mechanism to promote non-neuroendocrine plasticity and suggests that therapeutic approaches to activate STING could be selectively beneficial for SCLCs with NOTCH2 mutations.
Journal
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NOTCH1 (Notch 1) • NOTCH2 (Notch 2) • STING (stimulator of interferon response cGAMP interactor 1)
|
NOTCH2 mutation • NOTCH mutation
almost3years
Whole-genome and Transcriptome Sequencing Identified NOTCH2 and HES1 as Potential Markers of Response to Imatinib in Desmoid Tumor (Aggressive Fibromatosis): A Phase II Trial Study. (PubMed, Cancer Res Treat)
Imatinib was effective and well tolerated for advanced desmoid tumor treatment. Our results show that HES1, regulated by NOTCH2, as an indicator of sensitivity to imatinib, and an important therapeutic consideration for desmoid tumor.
P2 data • Journal
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NOTCH2 (Notch 2) • HES1 (Hes Family BHLH Transcription Factor 1)
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NOTCH2 mutation
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imatinib
3years
Upregulation of CD47 Expression in De Novo Diffuse Large B-Cell Lymphoma Is More Frequent in Activated B-Cell Type (ASH 2021)
The level of CD47 expression does not appear to predict OS in patients with DLBCL treated with R-CHOP. This study demonstrates that conventional immunohistochemical methods can readily identify DLBCL with high CD47 expression, and these patients may benefit from the use of anti-CD47 therapy.
IO biomarker
|
TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CCND1 (Cyclin D1) • BCL6 (B-cell CLL/lymphoma 6) • TET2 (Tet Methylcytosine Dioxygenase 2) • CD47 (CD47 Molecule) • NOTCH2 (Notch 2) • SIRPA (Signal Regulatory Protein Alpha)
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TP53 mutation • TET2 mutation • CD47 overexpression • NOTCH2 mutation • BCL6 translocation
|
Rituxan (rituximab)
3years
Preclinical
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NOTCH2 (Notch 2)
|
NOTCH2 mutation
3years
Revised International Prognostic Index and genetic alterations are associated with early failure to R-CHOP in patients with diffuse large B-cell lymphoma. (PubMed, Br J Haematol)
Here we analysed clinico-biological features in 373 DLBCL patients homogeneously treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP), in order to identify variables associated with early failure to treatment (EF), defined as primary refractoriness or relapse within 12 months from diagnosis. Mutations in NOTCH2, gains in 5p15·33 (TERT), 12q13 (CDK2), 12q14·1 (CDK4) and 12q15 (MDM2) showed predictive importance for EF independently from R-IPI. GEP studies showed that EF cases were significantly enriched in sets related to cell cycle regulation and inflammatory response, while cases in response showed over-representation of gene sets related to extra-cellular matrix and tumour microenvironment.
Clinical • Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • TERT (Telomerase Reverse Transcriptase) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • B2M (Beta-2-microglobulin) • NOTCH2 (Notch 2) • CDK2 (Cyclin-dependent kinase 2)
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NOTCH2 mutation • BCL2 rearrangement
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Rituxan (rituximab) • doxorubicin hydrochloride • vincristine
3years
NOTCH signaling in the pathogenesis of splenic marginal zone lymphoma-opportunities for therapy. (PubMed, Leuk Lymphoma)
These data make NOTCH signaling an appealing target for drug discovery in SMZL; however, prior efforts attempting to manipulate this pathway failed to demonstrate meaningful clinical benefit, or their safety profile prevented further development. In this review, we discuss the current knowledge of NOTCH implications in the pathogenesis and as a potential druggable target in SMZL.
Journal
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NOTCH1 (Notch 1) • NOTCH2 (Notch 2)
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NOTCH2 mutation
over3years
Risk-tailored treatment of splenic marginal zone lymphoma. (PubMed, Anticancer Drugs)
Patients with two or more score points have a median survival of <5 years. Watch and wait strategy is appropriate in low-risk and asymptomatic patients, whereas treatment of symptomatic patients ranges from splenectomy to rituximab monotherapy or associated with chemotherapy.
Journal
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NOTCH2 (Notch 2)
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NOTCH2 mutation
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Rituxan (rituximab)
over3years
Next-generation sequencing-based identification of EGFR and NOTCH2 complementary mutations in non-small cell lung cancer. (PubMed, Oncol Lett)
There was a negative correlation between EGFR and NOTCH2 mutations (correlation coefficient, -0.078; P=0.027). Thus, the present study highlights the importance of NOTCH2 mutations and might provide novel therapeutic options for patients with NSCLC who do not harbor EGFR mutations.
Journal • Next-generation sequencing
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • PTEN (Phosphatase and tensin homolog) • NOTCH2 (Notch 2)
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KRAS mutation • EGFR mutation • PTEN mutation • NOTCH2 mutation
almost4years
NOTCH and EZH2 collaborate to repress PTEN expression in breast cancer. (PubMed, Commun Biol)
Restoration of PTEN expression can be achieved with an EZH2 inhibitor (UNC1999), a γ-secretase inhibitor (Compound E), or knockdown of EZH2 or NOTCH. These findings elucidate a mechanism of transcriptional repression of PTEN induced by NOTCH1 or NOTCH2 alterations, and identifies actionable signaling pathways responsible for driving a large subset of poor-prognosis breast cancers.
Journal
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PTEN (Phosphatase and tensin homolog) • NOTCH1 (Notch 1) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • NOTCH2 (Notch 2) • HES1 (Hes Family BHLH Transcription Factor 1)
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PTEN mutation • NOTCH1 mutation • PTEN expression • NOTCH2 mutation
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UNC1999
almost4years
Analysis of mutations in cutaneous squamous cell carcinoma reveals novel genes and mutations associated with patient-specific characteristics and metastasis: a systematic review. (PubMed, Arch Dermatol Res)
Overall, novel mutations were identified and differences between mutation patterns in localized and metastatic SCCs were found. These findings may have clinical applications.
Clinical • Review • Journal • BRCA Biomarker
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TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • KMT2D (Lysine Methyltransferase 2D) • LRP1B (LDL Receptor Related Protein 1B) • KMT2C (Lysine Methyltransferase 2C) • NOTCH2 (Notch 2)
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TP53 mutation • NOTCH2 mutation
4years
Clinical and biological features of B-cell neoplasms with CDK6 translocations: an association with a subgroup of splenic marginal zone lymphomas displaying frequent CD5 expression, prolymphocytic cells, and TP53 abnormalities. (PubMed, Br J Haematol)
Overall survival was 82% at 10 years and not influenced by TP53 aberration. Our present findings suggest that most t(CDK6)+ neoplasms correspond to a particular subgroup of indolent marginal zone B-cell lymphomas with distinctive features.
Clinical • Journal
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TP53 (Tumor protein P53) • IGH (Immunoglobulin Heavy Locus) • NOTCH2 (Notch 2) • CDK6 (Cyclin-dependent kinase 6) • CD5 (CD5 Molecule)
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TP53 mutation • TP53 deletion • IGH mutation • NOTCH2 mutation • TP53 expression
over4years
Aggressive variant of splenic marginal zone lymphoma characterized using a cancer panel test and treated with rituximab-containing chemotherapy: A case report. (PubMed, Medicine (Baltimore))
This is a case of AV-SMZL in which a cancer panel test successfully detected genetic alterations that are potentially associated with its pathogenesis. These findings suggest that genetic analysis is useful for making diagnoses as well as for determining treatment strategies in AV-SMZL.
Clinical • Journal
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TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • NCOA4 (Nuclear Receptor Coactivator 4) • IL2 (Interleukin 2) • EPHA3 (EPH receptor A3)
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TP53 mutation • PTEN mutation • NOTCH2 mutation
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Rituxan (rituximab)
almost5years
Biological background of the genomic variations of cf-DNA in healthy individuals. (PubMed, Ann Oncol)
Our results also suggest the ineffectiveness for distinguishing clonal hematopoietic mutations of low variant allele frequency (≤0.1%) from tumor-derived mutations using conventional next-generation sequencing of blood cell DNA. However, an error correction model with an ultralow error rate and high coverage depth is required for blood cell DNA sequencing, which is difficult and costly to achieve with current technologies.
Clinical • Journal
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DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • NOTCH2 (Notch 2) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
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NOTCH2 mutation