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BIOMARKER:

EP300 mutation

i
Other names: EP300, E1A binding protein p300, p300, KAT3B, RSTS2
Entrez ID:
Related biomarkers:
3ms
Th2 Cells Are Associated with Tumor Recurrence Following Radiation. (PubMed, Cancers (Basel))
A pathway analysis of genes correlated with Th2 cells revealed the potential repression of the antitumor immune response and the activation of BRCA1-associated DNA damage repair in multiple cohorts. The Th2 infiltrates were enriched in the HPV/p16-negative HNSCC tumors and associated with LRR and mutations in CASP8, CREBBP/EP300, and pathways previously shown to impact the response to radiation.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • CREBBP (CREB binding protein) • EP300 (E1A binding protein p300) • CASP8 (Caspase 8)
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CREBBP mutation • CDKN2A negative • EP300 mutation
4ms
Phase classification
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CREBBP (CREB binding protein)
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CREBBP mutation • EP300 mutation
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mocetinostat (MGCD0103)
8ms
Preclinical and Early Clinical Results Indicate a Role for the Oral p300/CBP Inhibitor Inobrodib (CCS1477) in T-Cell Lymphoma (ASH 2023)
Together these data support the further development of inobrodib for the treatment of peripheral T cell lymphoma. Expansion continues with a focus on T-cell lymphomas, which may be driven by IRF4 and GATA3.
Preclinical
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EP300 (E1A binding protein p300) • IRF4 (Interferon regulatory factor 4) • GATA3 (GATA binding protein 3)
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EP300 mutation • IRF4 expression
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inobrodib (CCS1477)
8ms
The chromatin remodeling factors EP300 and TRRAP are novel SMYD3 interactors involved in the emerging 'nonmutational epigenetic reprogramming' cancer hallmark. (PubMed, Comput Struct Biotechnol J)
Of note, we validated these interactions in gastrointestinal cancer cell lines, including HCT-116 cells, which harbor a C-terminal truncating mutation in EP300, suggesting that EP300 binds to SMYD3 via its N-terminal region. While additional studies are required to ascertain the functional mechanisms underlying these interactions and their significance, the identification of two novel SMYD3 interactors involved in epigenetic cancer hallmark pathways adds important pieces to the puzzle of how SMYD3 exerts its oncogenic role.
Journal • BRCA Biomarker
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BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • EP300 (E1A binding protein p300) • SMYD3 (SET And MYND Domain Containing 3) • AMPK (Protein Kinase AMP-Activated Catalytic Subunit Alpha 1) • RBL2 (RB Transcriptional Corepressor Like 2)
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EP300 mutation
9ms
Novel Fusion Gene Aven-NUTM1 Induces Mice Myeloid Leukemia Vulnerable to HDAC Inhibitors (ASH 2023)
These results demonstrate that the AVEN-NUTM1 fusion gene can drive the development of myeloid leukemia in mice, AN's ability to bind and activate P300 is closely linked to its leukemogenicity, and that HDAC inhibitors are effective in targeting AN leukemia cells. The study provids valuable insights for the targeted treatment of NUTM1-related leukemia patients.
Preclinical
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EP300 (E1A binding protein p300) • NUTM1 (NUT Midline Carcinoma Family Member 1) • AVEN (Apoptosis And Caspase Activation Inhibitor)
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EP300 mutation
9ms
NGS-Based Stratification Refines the Risk Stratification in T-ALL and Identifies a Very High-Risk Subgroup of Patients (ASH 2023)
This model identifies 3 subgroups at CR1: a large favorable Risk (CR1-FAV) group (231/332, 70%) with CIR at 5 years estimated at 19% (95%CI:14%-24%) (Figure B), a subgroup of Adverse risk (CR1-ADV) patients (30/332, 9%) with a 5-year CIR of 68% (95%CI:46%-82%) and an Intermediate risk (CR1-INT) group (71/332, 21%) with a 5-year CIR of 37% (95%CI:26%-48%). Conclusion T-ALL NGS-based stratification combined with WBC and MRD evaluation sharpens the prognostic classification in T-ALL and identifies a new subgroup of adverse risk patients who should benefit from innovative therapeutic approaches.
Clinical • Next-generation sequencing
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • NOTCH1 (Notch 1) • IKZF1 (IKAROS Family Zinc Finger 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • EP300 (E1A binding protein p300) • PHF6 (PHD Finger Protein 6)
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TP53 mutation • PTEN mutation • DNMT3A mutation • FBXW7 mutation • PHF6 mutation • EP300 mutation
9ms
Integrated Analysis Focusing on Genome-Wide DNA Methylation in Pediatric Acute Promyelocytic Leukemia: The Jccg Study, JPLSG AML-P05 (ASH 2023)
While the prognosis of APL patients has dramatically improved with the use of all-trans retinoic acid and arsenic trioxide, cases of relapse still exist... DNA methylation analysis suggests that DNA methylation levels at specific CpG sites are effective biomarkers for the prognosis of pediatric APL. The presence of the EBF1 binding motif in the vicinity of these CpG sites suggests the involvement of EBF1 in prognosis.
Clinical • BRCA Biomarker • Epigenetic controller
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NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA2 (Breast cancer 2, early onset) • EP300 (E1A binding protein p300) • EBF1 (EBF Transcription Factor 1) • BAALC (BAALC Binder Of MAP3K1 And KLF4)
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NRAS mutation • EP300 mutation
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arsenic trioxide
9ms
Acetyl Transferase EP300 Deficiency Leads to Chronic Replication Stress in Adult T-Cell Leukemia/Lymphoma (ASH 2023)
However, EP300 deficient cells show a significant defect in innate immune system activation. Altogether these results suggest that mutations in EP300 cause chronic DNA replication stress, persistent genomic instability and innate immune system evasion underlie aggressive chemo-resistant tumorigenesis in humans.
Clinical • BRCA Biomarker
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BRCA2 (Breast cancer 2, early onset) • EP300 (E1A binding protein p300) • MRE11A (MRE11 homolog, double strand break repair nuclease) • POLD3 (DNA Polymerase Delta 3)
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EP300 mutation • BRCA2 expression
9ms
CD7 Chimeric Antigen Receptor T-Cell Therapy Bridging to Allogeneic Hematopoietic Stem Cell Transplantation Remarkably Improved Long-Term Disease-Free Survival in Refractory/Relapsed T-Cell Acute Lymphoblastic Leukemia/Lymphoma (ASH 2023)
Myeloablative conditioning regimens with either total body irradiation (TBI)/fludarabine (51, 56.7%) based or busulfan/fludarabine (39, 43.3%) based were applied...Cyclosporine, mycophenolate mofetil and short-term methotrexate were employed for graft-versus-host disease (GVHD) prophylaxis... Our study has demonstrated that CD7 CART followed by allo-HSCT has remarkably improved long-term DFS for chemotherapy-resistant T-ALL/LBL, and achieved comparable results in safety and efficacy with chemotherapy-sensitive disease post-transplant. Our study has also shown the profiles of somatic and germline gene mutations in r/r T-ALL/LBL, and identified some positive and negative impact factors for prognosis after transplant in this setting.
CAR T-Cell Therapy
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TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NOTCH1 (Notch 1) • JAK1 (Janus Kinase 1) • EP300 (E1A binding protein p300) • JAK3 (Janus Kinase 3) • CD7 (CD7 Molecule) • MED12 (Mediator Complex Subunit 12)
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TP53 mutation • ATM mutation • NOTCH1 mutation • JAK3 mutation • EP300 mutation
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methotrexate • fludarabine IV • busulfan • cyclosporine
12ms
Phase I Study of Entinostat, Atezolizumab, Carboplatin, and Etoposide in Previously Untreated Extensive-Stage Small Cell Lung Cancer, ETCTN 10399. (PubMed, Oncologist)
Addition of entinostat to atezolizumab, carboplatin, and etoposide is unsafe and resulted in early onset and severe neutropenia, thrombocytopenia. Further exploration of entinostat with carboplatin, etoposide, and atezolizumab should not be explored. (ClinicalTrials.gov Identifier: NCT04631029).
P1 data • Journal • PD(L)-1 Biomarker
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CREBBP (CREB binding protein) • EP300 (E1A binding protein p300)
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EP300 mutation
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Tecentriq (atezolizumab) • carboplatin • etoposide IV • Jingzhuda (entinostat)
12ms
Dermatological findings in Rubinstein-Taybi Syndrome. (PubMed, Ital J Dermatol Venerol)
Both susceptibility to the formation of keloids and pilomatricomas are the most often associated cutaneous features. In this review, we discuss the genetics, diagnosis, and clinical features in Rubinstein-Taybi Syndrome with a review of the major dermatological manifestations.
Journal
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CREBBP (CREB binding protein) • EP300 (E1A binding protein p300)
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CREBBP mutation • EP300 mutation
12ms
KAT6A::EP300 fusion in congenital myeloid sarcoma: Yet another novel molecular marker indicating spontaneous remission?: A case report. (PubMed, Medicine (Baltimore))
Even though the KAT6A::EP300 mutation in adults is a poor prognostic marker, a similar mutation in congenital AML has a higher likelihood of spontaneous remission. Hence, conservative management might be an initial management strategy for clinically stable patients.
Journal
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EP300 (E1A binding protein p300) • KAT6A (Lysine Acetyltransferase 6A) • NCOA2 (Nuclear Receptor Coactivator 2) • NCOA3 (Nuclear Receptor Coactivator 3)
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EP300 mutation
1year
Racial and sex differences in tumor genomics in urothelial carcinoma. (PubMed, Urol Oncol)
These differences highlight the importance of enriching cohorts for female and non-White patients in genomic studies and clinical trials, especially as we test the use of molecular biomarkers to personalize care for patients with bladder cancer.
Journal
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • HRAS (Harvey rat sarcoma viral oncogene homolog) • ARID1A (AT-rich interaction domain 1A) • EP300 (E1A binding protein p300) • NCOR1 (Nuclear Receptor Corepressor 1) • CHD6 (Chromodomain Helicase DNA Binding Protein 6)
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TP53 mutation • PIK3CA mutation • ARID1A mutation • HRAS mutation • EP300 mutation
1year
Targeted therapy using larotrectinib and venetoclax for the relapsed/refractory T-cell acute lymphoblastic leukemia harboring a cryptic ETV6-NTRK3 fusion. (PubMed, Mol Carcinog)
The leukemic clonal evolution might be revealed through transcriptome sequencing and overcome by drugs with universal targets. Our case demonstrated that both comprehensive profiling techniques (such as transcriptome sequencing, multiparameter flow cytometry, and digital droplet polymerase chain reaction) and a multimodality treatment strategy were critical for anticipating an early relapse and personalized therapy of R/R T-cell leukemia.
Journal • IO biomarker
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NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • EP300 (E1A binding protein p300) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK3 fusion • ETV6-NTRK3 fusion • EP300 mutation • NTRK3 positive • NTRK positive
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Venclexta (venetoclax) • Vitrakvi (larotrectinib)
1year
Study of Mocetinostat in Selected Patients With Mutations of Acetyltransferase Genes in Relapsed and Refractory Diffuse Large B-Cell Lymphoma and Follicular Lymphoma (clinicaltrials.gov)
P2, N=7, Terminated, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2023 --> May 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Oct 2023 --> May 2023; Lack of accrual
Trial completion date • Trial termination • Trial primary completion date
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CREBBP (CREB binding protein)
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CREBBP mutation • EP300 mutation
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mocetinostat (MGCD0103)
1year
STUDY OF GENETIC ALTERATIONS USING A CUSTOM LYMPHOID TARGETED NGS PANEL IN PATIENTS WITH FOLLICULAR LYMPHOMA: A PILOT STUDY (EHA 2023)
It was shown that genes involved in chromatin modification KMT2C , KMT2D , CREBBP , etc., are more likely tomutate in FL. Analysis of the functional enrichment of the gene set revealed a significant association of FL with chromatin remodeling pathways, PI3K-AKT and JAK-STAT. Mutation analysis, Follicular lymphoma, Gene mutation, Epigenetic
Clinical • Next-generation sequencing • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • KDR (Kinase insert domain receptor) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein) • FAT1 (FAT atypical cadherin 1) • EP300 (E1A binding protein p300) • GNAS (GNAS Complex Locus)
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ATM mutation • KMT2D mutation • EP300 mutation
over1year
P2 data • Journal
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CREBBP (CREB binding protein) • EP300 (E1A binding protein p300)
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EP300 mutation
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mocetinostat (MGCD0103)
over1year
Comprehensive genomic characterization of early-stage bladder cancer from 438 patients by whole genome- and exome sequencing (AACR 2023)
Here we investigated the landscape of DNA alterations in NMIBC in a large patient cohort of NMIBC samples with paired transcriptomic data and detailed clinical follow-up. We identified several novel genomic alterations; specifically, we showed that 15% of the tumors had genome doublings, and we identified a complex underlying copy number landscape of the region containing FGFR3.
Clinical • Tumor mutational burden
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • KMT2D (Lysine Methyltransferase 2D) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ERCC2 (Excision repair cross-complementation group 2) • KMT2C (Lysine Methyltransferase 2C) • KDM6A (Lysine Demethylase 6A) • STAG2 (Stromal Antigen 2) • EP300 (E1A binding protein p300) • GIGYF2 (GRB10 Interacting GYF Protein 2)
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TP53 mutation • HER-2 mutation • CDKN2A deletion • KMT2D mutation • RB1 mutation • CCND1 amplification • KDM6A mutation • EP300 mutation • GIGYF2 overexpression
over1year
CREBBP/EP300 disruption promotes tumor progression and confers synthetic lethality in anaplastic thyroid cancers (AACR 2023)
The recent approval of dabrafenib plus trametinib for the treatment of BRAFV600E-mutant ATCs improved the prognosis of a subset of patients, but ineligibility and acquired resistance still limit their use. Our findings prove the oncogenicity of HAT loss in thyroid cancer progression and support exploring synthetic lethality dependencies in CREBBP/EP300-mutant ATCs. In summary, we provide pre-clinical basis to inform genomics-driven and mechanism-oriented decisions for the clinical management of patients with HAT-altered ATC.
Synthetic lethality
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CREBBP (CREB binding protein) • EP300 (E1A binding protein p300)
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BRAF V600E • BRAF V600 • CREBBP mutation • EP300 mutation
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Mekinist (trametinib) • Tafinlar (dabrafenib)
over1year
Different treatment response in several head and neck squamous cell carcinoma (HNSCC) cell lines reflecting underlying genomic and molecular signatures (AACR 2023)
PI3K/mTOR dual inhibition, PI3Kalpha inhibitor, AKT inhibitor, FGFR inhibitor, ALK/IGF1R inhibitor, CDK4/6 inhibitor, BCl2 inhibitor, WEE1 inhibitor, ATR inhibitor, DNA-PK inhibitor, AT2AR inhibitor, Mcl-1 inhibitor, MEK1/2 inhibitor, EZH2 inhibitor, HDAC inhibitor, CDK9 inhibitor, DNMT3 inhibitor, BRD4/BET inhibitor, JAK2 inhibitor, CXCR4 inhibitor, FAK inhibitor, BTK inhibitor, eribulin, & VEGFR2/ PDGFR/FGFR or VEGFR2/c-MET/Axl triple blockage might be effective on TW2.6 and reverse treatment refractoriness, maybe through the inhibition of mesenchymal transformation, pRB, & PI3K/AKT /mTOR signaling and the modulation of stemness & PD1/PDL1 pathway...All cell lines will be tried to be categorized as TCGA subtypes for the reference of future drug combinations.Cell linesSCC25KBSASCAL27FaDuSCC15SCC9SCC4TW2.6Differ- entiationWellPoorPoorPoorPoorWellWellWellWell, but rapidly replicated, with high hyper-diploidy & complex rearrangementsHPV statusHPV 16/18HPV18--HPV 16/18--HPV 6/11-EGFR statusMediumLowHighHighMediumHighLowMedium to highUnknownDocetaxel sensitivity+++++++++++++ to +++++-+Cisplatin sensitivity+++++++++++++- to +-- to +5-FU sensitivity+++++++++++-+ to ++-- to +Afatinib sensitivity+++- to +-+++++ to +++++++++-Polo-like kinase Inhibitor sensitivity+++++++++++++ to +++- to +-- to +VEGFR2 Inhibitor sensitivity----+++++--++PI3K/ mTOR inhibitorAll cell lines sensitiveCDK4/6 Inhibitor response+++- to ++++++ to +++++++++++++ to +++Western blotsWeak p-AKT & VEGF-A, mild PDL1 and BMI-1, Gli-1(+)Weak p-AKT, mild PDL1 and strong VEGF-A & BMI-1, p16(+)Moderate p-AKT & BMI-1, high PDL1, mild VEGF-AHigh p-AKT & VEGF-A, mild PDL1 & BMI-1High VEGF-A, moderate p-AKT & PDL1, weak BMI-1, Gli-1(+)Weak p-AKT & VEGF-A, mild PDL1 & BMI-1Weak p-AKT, VEGF-A, & BMI-1, moderate PDL1Moderate p-AKT & VEGF-A, strong BMI-1, mild PDL1, Gli-1(+)High p-AKT, PDL1, & VEGF-A and moderate BMI-1NGSCCND1 gain, CDKN2A deletion, FRG1 mutation, HGF mutation, p53 mutation, ATR mutation, SMO mutation, RUNX1T1 mutationSTK11 mutation, PDGFRA mutation, IGF1 mutation, BCOR mutation, EGFR mutation, NOTCH1 mutation, MET mutation, IKZF1 mutation, NFKB1 mutation, DPYD mutation, FGFR4 mutation, BRCA1 mutation, MSH2 mutation, DNMT3A mutationKRAS mutation, MDM2 mutation, TMB-H, AXIN1 loss, RAD51D mutation, NOTCH1/2 mutation, ERBB4 mutation, PALB2 mutation, p53 mutation, POLE mutation, CASP8 mutation, BRCA2 mutation, RNF43 mutation, LRP1B mutation, MET mutationCDKN2A deletion, EGFR amplification, SMAD4 mutation, TMB-H, LRP1B mutation, APC mutation, CASP8 mutation, CREBBP mutation, PIK3CG mutation, NRAS mutation, ABL1 mutation, FGF23 mutation, HGF mutation, ATRX mutation, p53 mutation, ERBB2 mutation, ROS1 mutation, EP300 mutation, NRAS mutation, CDKN1A mutation, KDM6A mutation, FLT4 mutationCCND1 gain, CDKN2A deletion, FLCN mutation, TMB-H, LRP1B mutation, SMAD4 loss, SF3B1 mutation, FAT1 mutation, VHL mutation, NOTCH3 mutation, EPHA5 mutation, p53 mutation, ERCC2 mutationCCND1 gain, EGFR amplification, SMO mutation, ATR mutation, FAT1 loss, NTRK1 mutation, KMT2D mutation, p53 mutation, NOTCH3 mutationCDKN2A deletion, AXIN2 amplification, SMAD3 loss, HRAS mutation, ATR mutation, NF1 mutation. IGF1R mutation, FLCN mutation, KEAP1 mutation, ASXL1 mutation, PMS2 mutationCCND1 gain, NF1 loss, LRP1B mutation, NSD1 mutation, KMT2D mutation, p53 mutation, EPHA2 mutationFAT1 loss, CCND3/FGF10 amplification, PIK3CA H1047R mutation, STK11 mutation, RICTOR/FLCN amplification, VEGF-A amplification , TSC2 mutation, EPHB1 mutation, MAP2K4 mutation, KDM5A mutation, PDGFRB mutation, SETD2 mutation, RPTOR mutation, APC mutation, DDR2 mutation, ATM mutation, MDM2 mutation, p53 mutation, CDK12 mutation, HRAS mutation, MYC mutation, CDK8 mutation, ARID1B lossOutcomesBest; like TCGA CL (HPV+) subtypeLike TCGA basal subtype, but responded to particular treatments eachBasalBasalLike TCGA mesen-chymal subtype (HPV+)Like TCGA CL(HPV-) subtype, different characters between these 3 cell linesCL(HPV-) subtypeCL(HPV-) subtypeWorse; like TCGA EMT subtype (HPV-)Potential treatmentsAll sensitive maybe; Hedgehog inhibitor , HGF/c-MET inhibitor, and I/O could be tried(1) Taxane, cisplatin, PLKi (2) mTORi (3) IGF1Ri, METi, PDGFRi, FGFRi (4) Epigenetics (5) I/O(1) Taxane, cisplatin, 5-FU, PLKi (2) CDK4/6i (3) I/O (4) DDRi (5) KRASi, METi, HERi (6) p53 reactivator and MDM2/Mcl-1 inhibitor(1) Taxane, cisplatin, 5-FU, PLKi (2) CDK4/6i (3) Mild EGFRi response (4) I/O (5) NRASi, FGFRi, HGF/c-METi/ROS1i/HERi (6) p53 reactivator/DDRi/Epigenetics(1) Cisplatin, 5-FU (2) EGFRi and VEGFR2i (3) Weak to PLKi & CDK4/6i (4) I/O (5) mTORi (6) Ephi (7) DDR/Epigenetics (8) p53 reactivator (9) HIFi(1) Taxane and PLKi (2) EGFRi, VEGFR2i, CDK4/6i (3) NTRKi (4) Hedgehog inhibitor (5) DDRi, epigenetics,& p53 reactivator(1) Taxane &5-FU (2) EGFRi (3) HRASi (4) DDRi/Epigenetics (5) I/O (6) IGF1Ri (7) mTORi(1) EGFRi (2) CDK4/6i (3) I/O (4) Epigenetics (5) Ephi (6) p53 reactivator(1) CDK4/6 inhibitor (2) Multi-targeted VEGFR TKI (3) PI3K/AKT/mTOR inhibitor (4) ICIs combination (5) p53 reactivator/ DDR interventions/Epigenetics (6) Dasatinib, HRASi, EphB1/B4 interventions Further NGS analysis may translate these HNSCC cell lines to represent TCGA subtypes for the reference of future drug combinations, esp... Further NGS analysis may translate these HNSCC cell lines to represent TCGA subtypes for the reference of future drug combinations, esp. immunotherapy, basic/translational research, and animal models. LRP1B will be a potential ICIs efficacy biomarker in HNSCC.
Preclinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NOTCH1 (Notch 1) • NF1 (Neurofibromin 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • POLE (DNA Polymerase Epsilon) • AXL (AXL Receptor Tyrosine Kinase) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • CCND1 (Cyclin D1) • MDM2 (E3 ubiquitin protein ligase) • PALB2 (Partner and localizer of BRCA2) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • KMT2D (Lysine Methyltransferase 2D) • LRP1B (LDL Receptor Related Protein 1B) • FGFR4 (Fibroblast growth factor receptor 4) • MSH2 (MutS Homolog 2) • RNF43 (Ring Finger Protein 43) • CDK12 (Cyclin dependent kinase 12) • SMAD4 (SMAD family member 4) • IKZF1 (IKAROS Family Zinc Finger 1) • ERCC2 (Excision repair cross-complementation group 2) • PMS2 (PMS1 protein homolog 2) • VHL (von Hippel-Lindau tumor suppressor) • APC (APC Regulator Of WNT Signaling Pathway) • ATRX (ATRX Chromatin Remodeler) • TSC2 (TSC complex subunit 2) • IGF1R (Insulin-like growth factor 1 receptor) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • SMO (Smoothened Frizzled Class Receptor) • BCOR (BCL6 Corepressor) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • FAT1 (FAT atypical cadherin 1) • KDM6A (Lysine Demethylase 6A) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma) • NOTCH3 (Notch Receptor 3) • ARID1B (AT-Rich Interaction Domain 1B) • EP300 (E1A binding protein p300) • FLT4 (Fms-related tyrosine kinase 4) • IGF1 (Insulin-like growth factor 1) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • RAD51D (RAD51 paralog D) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • EPHA2 (EPH receptor A2) • BMI1 (BMI1 proto-oncogene, polycomb ring finger) • CASP8 (Caspase 8) • CCND3 (Cyclin D3) • BRD4 (Bromodomain Containing 4) • DDR2 (Discoidin domain receptor 2) • FLCN (Folliculin) • KDM5A (Lysine Demethylase 5A) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DPYD (Dihydropyrimidine Dehydrogenase) • EPHA5 (EPH Receptor A5) • EPHB1 (EPH Receptor B1) • FGF10 (Fibroblast Growth Factor 10) • FGF23 (Fibroblast Growth Factor 23) • MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4) • SMAD3 (SMAD Family Member 3)
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TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • EGFR mutation • TMB-H • NRAS mutation • PIK3CA mutation • EGFR amplification • ATM mutation • PIK3CA H1047R • STK11 mutation • DNMT3A mutation • PALB2 mutation • POLE mutation • NF1 mutation • NOTCH1 mutation • ASXL1 mutation • CDKN2A deletion • BCL2 overexpression • KEAP1 mutation • SF3B1 mutation • CDKN2A mutation • KMT2D mutation • CDK12 mutation • LRP1B mutation • VHL mutation • PIK3CA amplification • HRAS mutation • APC mutation • ATR mutation • ATRX mutation • CCND1 amplification • PDGFRA mutation • CREBBP mutation • MSH2 mutation • RNF43 mutation • ROS1 mutation • SMAD4 mutation • BCOR mutation • FGFR4 mutation • KDM6A mutation • RAD51D mutation • TSC2 mutation • FAT1 mutation • MYC mutation • ARID1B mutation • NOTCH3 mutation • PMS2 mutation • SMO mutation • IKZF1 mutation • MDM2 mutation • NTRK1 mutation • EP300 mutation • ERBB4 mutation • NSD1 mutation • PIK3CA H1047R + PIK3C2B amplification • PIK3CG mutation • SETD2 mutation • EPHA5 mutation • EPHB1 mutation • ERCC2 mutation • FGF10 amplification • FGF23 mutation • FLCN mutation • HGF mutation • PDGFRB mutation • RAD51 mutation
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cisplatin • Gilotrif (afatinib) • dasatinib • 5-fluorouracil • Halaven (eribulin mesylate)
over1year
Racial/ethnic and sex differences in somatic cancer gene mutations among patients with early-onset colorectal cancer. (PubMed, Cancer Discov)
Males and females with non-hypermutated CRC had different trends in EP300 mutations by age group. These findings define genomic patterns of early-onset non-hypermutated CRC by race/ethnicity and sex, which yields novel biological clues into early-onset CRC disparities.
Journal
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • LRP1B (LDL Receptor Related Protein 1B) • RNF43 (Ring Finger Protein 43) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • FAT1 (FAT atypical cadherin 1) • EP300 (E1A binding protein p300) • FLT4 (Fms-related tyrosine kinase 4) • WRN (WRN RecQ Like Helicase) • SMAD2 (SMAD Family Member 2)
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KRAS mutation • BRAF mutation • PIK3CA mutation • LRP1B mutation • ATRX mutation • RNF43 mutation • EP300 mutation
over1year
CAR-T therapy followed by allogeneic hematopoietic stem cell transplantation for refractory/relapsed acute B lymphocytic leukemia: Long-term follow-up results. (PubMed, Front Oncol)
Germline EP300 mutation and tumor somatic TP53 mutation are poor prognostic factors for posttransplant recurrence and survival in r/r B-ALL patients achieving CR after CAR-T therapy. The prognostic risk factors should be considered in adjusting treatment strategies to improve the efficacy of clinical diagnosis and treatment.
Journal • IO biomarker
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TP53 (Tumor protein P53) • EP300 (E1A binding protein p300)
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TP53 mutation • EP300 mutation
over1year
Experimental analysis of bladder cancer-associated mutations in EP300 identifies EP300-R1627W as a driver mutation. (PubMed, Mol Med)
In summary, our work defines a driver role of EP300-R1627W in bladder cancer development and progression.
Journal
|
TP53 (Tumor protein P53) • EP300 (E1A binding protein p300) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
|
TP53 mutation • EP300 mutation
over1year
Effects of the Omega-3 Fatty Acid DHA on histone and p53 acetylation in Diffuse Large B-Cell Lymphoma. (PubMed, Biochem Cell Biol)
qRT-PCR results revealed significant changes in expression of multiple genes, including increased expression of CREBBP and of PRDM1 (required for differentiation into plasma cells or memory B-cells). Taken together, our results provide (to our knowledge) the first characterization of the epigenetic effects of omega-3 fatty acids in DLBCL.
Journal
|
TP53 (Tumor protein P53) • CREBBP (CREB binding protein) • EP300 (E1A binding protein p300) • PRDM1 (PR/SET Domain 1)
|
CREBBP mutation • EP300 mutation
over1year
P62SQSTM1 Affects Interacting Substrates MDM2, MDMX and Casein Kinase 1alpha to Yield Protection of Beta-Catenin Along with p53 Silencing for Refractory AML (ASH 2022)
Primary p53-wild-type AML blasts or isogenic cell lines were treated in vitro with graded doses of the MDM2 inhibitors Pevonedistat (PEVO) or Siremadlin, either added alone, or in combination with Ixazomib at pharmacokinetically-achievable dose ranges typical in patients. In addition, a combination of PEVO/Ixazomib was as effective for apoptosis as was Flt3 inhibitor among certain Flt3mutant primary AML blasts. A clinical test of this strategy is warranted in high-risk relapsed/refractory p53WT/p62SQSTM1-expressing AML.
IO biomarker
|
TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • BCL2 (B-cell CLL/lymphoma 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • EP300 (E1A binding protein p300) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • SQSTM1 (Sequestosome 1) • HOTAIR (HOX Transcript Antisense RNA) • NQO1 (NAD(P)H dehydrogenase, quinone 1) • CSNK1A1 (Casein Kinase 1 Alpha 1) • PRDM16 (PR/SET Domain 16)
|
TP53 mutation • FLT3 mutation • TP53 wild-type • EP300 mutation • HOTAIR overexpression
|
Ninlaro (ixazomib) • pevonedistat (MLN4924) • siremadlin (HDM201)
over1year
The Cause and Consequence of Replication Stress in Adult T-Cell Leukemia (ASH 2022)
These results raise the possibility of the contribution of a suppressed innate immune response, a phenomenon seen in many fast-progressing cancers, to the etiology of NA-ATLL. In addition to increasing our understanding of the mechanisms contributing to ATLL in general, the results from this study have helped identify new mechanism-based treatment regimens that could target the replicative and innate immune system vulnerabilities observed in North American ATLL patients.
Clinical
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • EP300 (E1A binding protein p300) • STING (stimulator of interferon response cGAMP interactor 1) • MRE11A (MRE11 homolog, double strand break repair nuclease)
|
MYC expression • EP300 mutation
over1year
Identification of Genetic Subtypes in Follicular Lymphoma (ASH 2022)
Here, we identified novel genetic subtypes that are distinguishable not just by unique sets of mutations, but also by their clinical associations and methylation profiles. The novel genetic profiles shed light on core pathways distinctly tied to each subtype. Targeted DNA sequencing of a limited gene panel represents a potentially accessible method of subtyping FL in the clinical setting, with implications for the understanding of responses to targeted therapy.
Tumor Mutational Burden
|
TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CREBBP (CREB binding protein) • EP300 (E1A binding protein p300) • TNFAIP3 (TNF Alpha Induced Protein 3) • GNA13 (G Protein Subunit Alpha 13) • TNFRSF14 (TNF Receptor Superfamily Member 14) • STAT6 (Signal transducer and activator of transcription 6) • TNFRSF18 (TNF Receptor Superfamily Member 18) • ATP6AP1 (ATPase H+ Transporting Accessory Protein 1)
|
TP53 mutation • TMB-L • EZH2 mutation • EP300 mutation • GNA13 mutation • TNFRSF14 mutation
over1year
Mutational profiling of circulating tumor DNA and clinical characteristics in lymphoma: Based on next generation sequencing. (PubMed, Mol Carcinog)
Moreover, in MBN and DLBCL datasets, patients with TP53 mutation had a significantly shorter OS (all p < 0.05) in both circulating free DNA and tumor tissue. The mutations (no SNP) of NOTCH1 (all p < 0.05) significantly contributed to worse OS in the two cohorts.
Journal • Next-generation sequencing • IO biomarker • Circulating tumor DNA
|
TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NOTCH1 (Notch 1) • EP300 (E1A binding protein p300) • JAK3 (Janus Kinase 3) • IRF8 (Interferon Regulatory Factor 8) • BTG2 (BTG Anti-Proliferation Factor 2)
|
TP53 mutation • JAK3 mutation • EP300 mutation
almost2years
A genetic map of the chromatin regulators to drug response in cancer cells. (PubMed, J Transl Med)
The CRs genetic interaction map provides a rich resource to investigate cancer-associated CRs genetic interaction and proposes a powerful strategy of biomarker discovery to guide the rational use of agents in cancer therapy.
Journal
|
MSH6 (MutS homolog 6) • EP300 (E1A binding protein p300) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
|
EP300 mutation
|
Zolinza (vorinostat)
almost2years
Study of Mocetinostat in Selected Patients With Mutations of Acetyltransferase Genes in Relapsed and Refractory Diffuse Large B-Cell Lymphoma and Follicular Lymphoma (clinicaltrials.gov)
P2, N=7, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2022 --> Oct 2023 | Trial primary completion date: Oct 2022 --> Oct 2023
Trial completion date • Trial primary completion date
|
CREBBP (CREB binding protein)
|
CREBBP mutation • EP300 mutation
|
mocetinostat (MGCD0103)
2years
Study to Evaluate CCS1477 in Advanced Tumours (clinicaltrials.gov)
P1/2, N=350, Recruiting, CellCentric Ltd. | N=200 --> 350 | Trial completion date: Jun 2022 --> Mar 2024 | Trial primary completion date: Jun 2022 --> Mar 2024
Enrollment change • Trial completion date • Trial primary completion date
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • AR (Androgen receptor) • ARID1A (AT-rich interaction domain 1A) • CREBBP (CREB binding protein)
|
ARID1A mutation • CREBBP mutation • EP300 mutation
|
Lynparza (olaparib) • Tecentriq (atezolizumab) • Xtandi (enzalutamide capsule) • abiraterone acetate • Nubeqa (darolutamide) • inobrodib (CCS1477)
2years
Clinical features and next-generation sequencing landscape of essential thrombocythemia, prefibrotic primary myelofibrosis, and overt fibrotic primary myelofibrosis: a Chinese monocentric retrospective study. (PubMed, J Cancer Res Clin Oncol)
The results of this study indicated that a comprehensive evaluation of BM features, clinical phenotypes, haematologic parameters, and molecular profiles is needed for the accurate diagnosis and treatment of ET, pre-PMF, and overt PMF patients.
Retrospective data • Journal • Next-generation sequencing
|
TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • WT1 (WT1 Transcription Factor) • EP300 (E1A binding protein p300)
|
TP53 mutation • ASXL1 mutation • LDH-L • WT1 overexpression • EP300 mutation
2years
Whole-Genome/Exome Sequencing Uncovers Mutations and Copy Number Variations in Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System. (PubMed, Front Genet)
Notably, 1q31.3 amplification was closely associated with the poor prognosis of PCNSL patients. This study further characterizes the genomic landscape of primary CNS DLBCL using WGS/WES, which provides insight into understanding the pathogenesis of PCNSL and fosters new ideas for the targeted treatment of PCNSL.
Journal
|
MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • ETV6 (ETS Variant Transcription Factor 6) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • EP300 (E1A binding protein p300) • PIM1 (Pim-1 Proto-Oncogene) • IGLL5 (Immunoglobulin Lambda Like Polypeptide 5) • BTG2 (BTG Anti-Proliferation Factor 2) • PCLO (Piccolo Presynaptic Cytomatrix Protein)
|
KMT2D mutation • EP300 mutation
2years
GENOTYPING ON CIRCULATING TUMOR DNA IMPROVES MUTATION DETECTION RATE IN HIGH-RISK DIFFUSE LARGE B-CELL LYMPHOMA (EHA 2022)
In fact, 35.3% (6/17) MCD DLBCLs were only identified by ctDNA but not by gDNA, suggesting the addition of ctDNA genotyping substantially improved the detection rate of MCD subtype (figure 1). Conclusion Our study highlights the clinical application of ctDNA, in particular in patients with high-risk and early relapsed or refractory diseases, where ctDNA analysis represents a complementary approach to tissue biopsy gDNA genotyping.
Circulating tumor DNA
|
TP53 (Tumor protein P53) • B2M (Beta-2-microglobulin) • EP300 (E1A binding protein p300) • PRDM1 (PR/SET Domain 1)
|
TP53 mutation • EP300 mutation • PRDM1 mutation
2years
A p300/GATA6 axis determines differentiation and Wnt dependency in pancreatic cancer models. (PubMed, J Clin Invest)
Mechanistically, loss of EP300 directly down-regulated GATA6 expression, thereby silencing the GATA6-regulated differentiation program and leading to a phenotypic transition from the classical subtype to the dedifferentiated basal-like/squamous subtype of pancreatic cancer. EP300 mutation and loss of GATA6 function bypassed the anti-differentiation activity of Wnt signaling, rendering these cancer cells resistant to Wnt inhibition. .
Preclinical • Journal
|
RNF43 (Ring Finger Protein 43) • CREBBP (CREB binding protein) • EP300 (E1A binding protein p300) • GATA6 (GATA Binding Protein 6) • AXIN1 (Axin 1)
|
RNF43 mutation • EP300 mutation • GATA6 expression
over2years
KAT6A-EP300 MUTATION IN CONGENITAL MYELOID SARCOMA YET ANOTHER MARKER FOR SPONTANEOUS REMISSION? (ASPHO 2022)
This is the second known reported case with KAT6A/EP300 fusion undergoing spontaneous remission. Congenital AML with skin involvement with this mutation has the potential for spontaneous remission.
Clinical
|
CREBBP (CREB binding protein) • CD4 (CD4 Molecule) • EP300 (E1A binding protein p300) • CD68 (CD68 Molecule)
|
EP300 mutation
|
FoundationOne® CDx
over2years
KIX domain determines a selective tumor-promoting role for EP300 and its vulnerability in small cell lung cancer. (PubMed, Sci Adv)
Blockade of KIX-mediated interactions inhibits SCLC development in mice and cell growth. This study unravels domain-specific roles for EP300 in SCLC and unique vulnerability of the EP300 KIX domain for therapeutic intervention.
Journal
|
CREBBP (CREB binding protein) • EP300 (E1A binding protein p300)
|
EP300 mutation
over2years
The Correlation analysis of driver genes of JAK-STAT signaling pathway with tumor immune microenvironment and prognosis in hepatocellular carcinoma (AACR 2022)
STAT3 and EP300 are driver genes of JAK-STAT signaling pathway in HCC. The JAK-STAT pathway mutation was associated with M2 macrophage infiltration and increased PD-L1 expression of macrophages, suggesting a poor prognosis.
PD(L)-1 Biomarker • IO biomarker
|
JAK1 (Janus Kinase 1) • STAT3 (Signal Transducer And Activator Of Transcription 3) • EP300 (E1A binding protein p300)
|
PD-L1 expression • STAT3 mutation • EP300 mutation
over2years
Activity and tolerability of combination of venetoclax with the Aurora kinase B Inhibitor AZD2811 in preclinical diffuse large B-cell lymphoma models (AACR 2022)
The current standard of care is comprised of a regimen of 4 drugs (cyclophosphamide, doxorubicin, vincristine, and prednisone) combined with immunotherapy using a chimeric mAb against the protein CD20 (rituximab), R-CHOP. While both monotherapies were unable to prevent progressive tumor growth, a combination dosing regimen of AZD2811 and venetoclax drove progressive tumor regression resulting in statistically significant complete regression (98% regression) by the third week of dosing. These results suggest combining AZD2811 with venetoclax has potential to be active in DLBCL patients.
Preclinical • IO biomarker
|
PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • EP300 (E1A binding protein p300) • FLT4 (Fms-related tyrosine kinase 4) • AURKB (Aurora Kinase B)
|
PTEN mutation • EP300 mutation
|
Venclexta (venetoclax) • Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • vincristine • barasertib-HQPA (AZD2811)
over2years
A novel computational framework predicts synthetic lethal interactions between key regulators of the DNA damage response and chromatin modifiers (AACR 2022)
The concept of synthetic lethality (SL) has made a pivotal impact for the development of the anti-cancer drug olaparib, the first approved agent targeting the DNA Damage Response (DDR)...Here, we focused on discovering novel SL relationships for the key DDR regulators ATM, ATR and DNA-PK. Our results provide not only new biomarker hypotheses for further validation, but also suggest that cancers with a high mutation rate in chromatin modifying genes may be efficiently targeted by DDRi.
PARP Biomarker • Synthetic lethality
|
ATR (Ataxia telangiectasia and Rad3-related protein) • EP300 (E1A binding protein p300)
|
EP300 mutation
|
Lynparza (olaparib)