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    BIOMARKER:

    SMARCA4 mutation

    i
    Other names: SMARCA4, SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 4, Mitotic Growth And Transcription Activator, ATP-Dependent Helicase SMARCA4, Global Transcription Activator Homologous Sequence, Transcription Activator BRG1, Sucrose Nonfermenting-Like 4, BRG1-Associated Factor 190A, Protein Brahma Homolog 1, BRM/SWI2-Related Gene 1, Homeotic Gene Regulator, Brahma Protein-Like 1, Nuclear Protein GRB1, Protein BRG-1, SNF2-Like 4, SNF2-Beta, BAF190A, SNF2L4, BRG1,BAF190, SNF2LB, HSNF2b, MRD16, RTPS2, SNF2B, CSS4, SNF2, SWI2
    Entrez ID:
    6597
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    3d
    A Study of Tazemetostat in Adult Participants With Soft Tissue Sarcoma (clinicaltrials.gov)
    P2, N=267, Completed, Epizyme, Inc. | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Feb 2024
    Trial completion • Trial completion date
    |
    CD34 (CD34 molecule) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
    |
    SMARCA4 mutation
    |
    Tazverik (tazemetostat)
    16d
    SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic features. (PubMed, Blood)
    Here we demonstrate that EBV- BL comprises two subsets of cases based on SOX11 expression. The mutual exclusion of SOX11 and EBV, and the association of SOX11 with a specific genetic landscape suggest a role of SOX11 in the early pathogenesis of BL.
    Journal
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • ID3 (Inhibitor Of DNA Binding 3, HLH Protein) • SOX11 (SRY-Box Transcription Factor 11) • VCAM1 (Vascular Cell Adhesion Molecule 1)
    |
    MYC expression • SMARCA4 mutation • MYC translocation • SOX11 expression
    16d
    Redoxhigh phenotype mediated by KEAP1/STK11/SMARCA4/NRF2 mutations diminishes tissue-resident memory CD8+ T cells and attenuates the efficacy of immunotherapy in lung adenocarcinoma. (PubMed, Oncoimmunology)
    The redoxhigh phenotype in LUAD is predominantly driven by mutations in KEAP1, STK11, NRF2, and SMARCA4. This phenotype diminishes the number of tissue-resident memory CD8+ T cells and attenuates the efficacy of ICIs.
    Journal • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • CD8 (cluster of differentiation 8) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)
    |
    EGFR mutation • STK11 mutation • KEAP1 mutation • SMARCA4 mutation • NFE2L2 mutation
    18d
    SMARCA4 Mutations in Gastroesophageal Adenocarcinoma: An Observational Study via a Next-Generation Sequencing Panel. (PubMed, Cancers (Basel))
    These results serve as the first comprehensive examination of the relationship between SMARCA4ms and clinical outcomes in GEA.
    Observational data • Journal • Next-generation sequencing • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • FANCA (FA Complementation Group A) • FANCL (FA Complementation Group L)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • HER-2 mutation • PTEN mutation • ARID1A mutation • SMARCA4 mutation
    26d
    Development of an orally bioavailable mSWI/SNF ATPase degrader and acquired mechanisms of resistance in prostate cancer. (PubMed, Proc Natl Acad Sci U S A)
    AU-24118 demonstrated tumor regression in a model of castration-resistant prostate cancer (CRPC) which was further enhanced with combination enzalutamide treatment, a standard of care androgen receptor (AR) antagonist used in CRPC patients. The ABCB1 inhibitor, zosuquidar, reversed resistance to all three PROTAC degraders tested. Combined, these findings position mSWI/SNF degraders for clinical translation for patients with enhancer-driven cancers and define strategies to overcome resistance mechanisms that may arise.
    Journal
    |
    AR (Androgen receptor) • PBRM1 (Polybromo 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    SMARCA4 mutation • ABCB1 overexpression • ABCB1 expression
    |
    Xtandi (enzalutamide capsule)
    26d
    Synthetic lethality: targeting SMARCA2 ATPase in SMARCA4-deficient tumors - a review of patent literature from 2019-30 June 2023. (PubMed, Expert Opin Ther Pat)
    Most early compounds are weakly selective, but these efforts have culminated in the first dual SMARCA2/SMARCA4 ATPase inhibitor to enter clinical trials. Data from the ongoing clinical trials, as well as continued advancement of SMARCA2-selective ATPase inhibitors, are anticipated to significantly impact the field of therapies, targeting SMARCA4-deficient tumors.
    Review • Journal • Synthetic lethality
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    SMARCA4 mutation
    1m
    A Study of Tazemetostat in Adult Participants With Soft Tissue Sarcoma (clinicaltrials.gov)
    P2, N=267, Active, not recruiting, Epizyme, Inc. | Trial primary completion date: Jun 2024 --> Feb 2024
    Trial primary completion date
    |
    CD34 (CD34 molecule) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
    |
    SMARCA4 mutation
    |
    Tazverik (tazemetostat)
    2ms
    Evaluate the Safety and Clinical Activity of HH2853 (clinicaltrials.gov)
    P1/2, N=168, Recruiting, Haihe Biopharma Co., Ltd. | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1)
    |
    ARID1A mutation • BAP1 mutation • EZH2 mutation • SMARCA4 mutation
    |
    HH2853
    2ms
    SWI/SNF regulation of germinal center fate and lymphomagenesis. (PubMed, Cancer Cell)
    and Deng et al. find that loss of ARID1A or SMARCA4 contributes to lymphomagenesis by causing B cells to aberrantly re-enter germinal centers where they undergo repeated rounds of proliferation and somatic hypermutation.
    Journal
    |
    ARID1A (AT-rich interaction domain 1A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    ARID1A mutation • SMARCA4 mutation
    2ms
    SMARCA4 deficiency and mutations are frequent in large cell lung carcinoma and are prognostically significant. (PubMed, Pathology)
    Taken together, the high incidence of SMARCA4 aberrations in LCC may indicate its diagnostic and prognostic value. Our study established the necessity of SMARCA4 IHC in the identification of SMARCA4-aberrant tumours, and this may be of particular importance in LCC and tumours without known driver events.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • NKX2-1 (NK2 Homeobox 1)
    |
    EGFR mutation • SMARCA4 mutation
    2ms
    SMARCA4 loss and mutated β-catenin induce proliferative lesions in the murine embryonic cerebellum. (PubMed, J Neurosci)
    This observation could have important implications for WNT medulloblastoma patients, who are frequently affected by both alterations with the functional role of SMARCA4 mutations in tumorigenesis not deciphered so far. Additionally, this work highlights divergence of mouse phenotypes after brain-specific activation of WNT signaling from previously published studies and proposes potential reasons for varying recombination using the brain lipid binding protein (Blbp)-cre mouse strain.
    Preclinical • Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • SOX2
    |
    CTNNB1 mutation • SMARCA4 mutation
    2ms
    HER2 Gene Amplification in Endometrial Clear Cell Carcinoma:a Mono-Institutional Study of 23 Cases in China (USCAP 2024)
    In endometrial clear cell carcinoma, we observed 8.7% of tumors with HER2 gene amplification. The HER2 immunohistochemical staining appears to be consistent with the HER2 gene amplification. It needs further cases to be validated.
    Clinical • MSi-H Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • MSI (Microsatellite instability) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ARID1A (AT-rich interaction domain 1A) • NOTCH1 (Notch 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • ARID1B (AT-Rich Interaction Domain 1B) • SPOP (Speckle Type BTB/POZ Protein) • ERCC5 (ERCC Excision Repair 5 Endonuclease 2) • ZNF217 (Zinc Finger Protein 217) • RECQL4( RecQ Like Helicase 4) • PIK3R2 (Phosphoinositide-3-Kinase Regulatory Subunit 2 )
    |
    MSI-H/dMMR • HER-2 overexpression • HER-2 amplification • ARID1A mutation • SMARCA4 mutation
    |
    PATHWAY antiHer2/neu (4B5) Rabbit Monoclonal Primary Antibody
    3ms
    Recurrence/prognosis estimation using a molecularly positive surgical margin-based model calls for alternative curative strategies in pIIIA/N2 NSCLC. (PubMed, Mol Oncol)
    Notably, mutational profiling through broad-panel NGS could more sensitively detect residual tumors than the conventional histologic methods. Adjuvant CT and adjuvant CRT exhibited no significant difference in eliminating locoregional recurrence risk for stage pIIIA/N2 NSCLC patients with molecularly positive surgical margins.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • TYK2 (Tyrosine Kinase 2) • SMARCD3 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily D, Member 3)
    |
    HER-2 mutation • SMARCA4 mutation
    3ms
    Thoracic SMARCA4-deficient undifferentiated tumor: A clinicopathological and prognostic analysis of 35 cases and immunotherapy efficacy. (PubMed, Lung Cancer)
    Thoracic SMARCA4-UTs exhibited an aggressive clinical course, presented solid architecture with or without necrosis and/or rhabdoid morphology, and frequently expressed CD34 and synaptophysin. Some thoracic SMARCA4-UTs appear to be associated with responsiveness to immunotherapy, suggesting the need for validation in larger series.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CD34 (CD34 molecule) • SYP (Synaptophysin)
    |
    PD-L1 expression • SMARCA4 mutation
    3ms
    Cytopathological characteristics of SMARCA4-deficient thoracic undifferentiated tumors in serous effusion (PubMed, Zhonghua Bing Li Xue Za Zhi)
    This tumor thus warrants careful consideration. Accurate diagnosis can greatly improve early diagnosis and treatment of these tumors.
    Journal • PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • CD34 (CD34 molecule) • SALL4 (Spalt Like Transcription Factor 4) • SYP (Synaptophysin)
    |
    TP53 mutation • HER-2 amplification • MET amplification • STK11 mutation • PD-L1 negative • CDKN2A mutation • MET mutation • BRCA2 deletion • SMARCA4 mutation • BRCA1 deletion
    |
    PD-L1 IHC 22C3 pharmDx
    3ms
    Clinicopathological features of SMARCA4-deficient lung adenocarcinoma: a study of 42 cases (PubMed, Zhonghua Bing Li Xue Za Zhi)
    It is necessary to identify this subset of lung adenocarcinoma by carrying out BRG1 stain routinely on lung adenocarcinoma. These patients can then be identified and benefit from targeted therapies.
    Journal • Retrospective data • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • TTF1 (Transcription Termination Factor 1) • NKX2-1 (NK2 Homeobox 1) • NAPSA (Napsin A Aspartic Peptidase)
    |
    TP53 mutation • KRAS mutation • EGFR mutation • STK11 mutation • RET mutation • KEAP1 mutation • MET mutation • SMARCA4 mutation • NKX2-1 expression • TTF1 expression
    |
    PD-L1 IHC 22C3 pharmDx
    4ms
    A Study of PRT3645 in Participants With Select Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=22, Active, not recruiting, Prelude Therapeutics | Recruiting --> Active, not recruiting | N=61 --> 22
    Enrollment closed • Enrollment change • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    KRAS mutation • ER positive • HER-2 negative • TP53 wild-type • CDKN2A deletion • RAS wild-type • SMARCA4 mutation • IDH wild-type
    |
    PRT3645
    4ms
    Characterization of a Preclinical In Vitro Model Derived from a SMARCA4-Mutated Sinonasal Teratocarcinosarcoma. (PubMed, Cells)
    Focusing on mutated SMARCA4 as the therapeutic target, growth inhibition assays showed a strong response to the CDK4/6 inhibitor palbociclib, but much less to the EZH1/2 inhibitor valemetostat. In conclusion, cell line TCS627 carries both histologic and genetic features characteristic of TCS and is a valuable model for both basic research and preclinical testing of new therapeutic options for treatment of TCS patients.
    Preclinical • Journal
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • TET2 (Tet Methylcytosine Dioxygenase 2) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • NOTCH3 (Notch Receptor 3) • STAG2 (Stromal Antigen 2) • ARID2 (AT-Rich Interaction Domain 2) • WNT7A (Wnt Family Member 7A)
    |
    TET2 mutation • SMARCA4 mutation • STAG2 mutation
    |
    Ibrance (palbociclib) • Ezharmia (valemetostat)
    4ms
    PROTACs Targeting BRM (SMARCA2) Afford Selective In Vivo Degradation over BRG1 (SMARCA4) and Are Active in BRG1 Mutant Xenograft Tumor Models. (PubMed, J Med Chem)
    Subsequent PK/PD analysis established a need to achieve strong BRM degradation (>95%) in order to trigger meaningful antitumor activity in vivo. Intratumor quantitation of mRNA associated with two genes whose transcription was controlled by BRM (PLAU and KRT80) also supported this conclusion.
    Preclinical • Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • PLAU (Plasminogen Activator)
    |
    SMARCA4 mutation
    4ms
    Molecular and Pathologic Characterization of YAP1-Expressing Small Cell Lung Cancer Cell Lines Leads to Reclassification as SMARCA4-Deficient Malignancies. (PubMed, Clin Cancer Res)
    SMARCA4-mutant SCLC-Y cell lines exhibit characteristics consistent with SMARCA4-deficient malignancies rather than SCLC. Our findings suggest that, unlike ASCL1, NEUROD1, and POU2F3, YAP1 is not a subtype defining transcription factor in SCLC.
    Preclinical • Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • YAP1 (Yes associated protein 1) • POU2F3 (POU Class 2 Homeobox 3) • ASCL1 (Achaete-Scute Family BHLH Transcription Factor 1) • NEUROD1 (Neuronal Differentiation 1)
    |
    SMARCA4 mutation
    4ms
    Impact of Mutations in Subunit Genes of the Mammalian SWI/SNF Complex on Immunological Tumor Microenvironment. (PubMed, Cancer Genomics Proteomics)
    These results suggest that immune tumor microenvironment status, such as mature B cell recruitment featuring the TLS gene signature and immune activation mediated by cancer signal down-regulation, might contribute to the classification of SMARCA4 gene-mutated tumors as immune checkpoint blockade therapy-sensitive target tumors.
    Journal • IO biomarker
    |
    CD20 (Membrane Spanning 4-Domains A1) • PBRM1 (Polybromo 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CD38 (CD38 Molecule) • ARID2 (AT-Rich Interaction Domain 2) • CCR7 (Chemokine (C-C motif) receptor 7) • CD27 (CD27 Molecule) • AURKB (Aurora Kinase B) • IRF4 (Interferon regulatory factor 4) • CD40LG (CD40 ligand)
    |
    PBRM1 mutation • SMARCA4 mutation • TLS gene signature
    4ms
    SMARCA4/BRG1-deficient Uterine Neoplasm With Hybrid Adenosarcoma and Carcinoma Features: Expanding the Molecular-morphologic Spectrum of SMARCA4-driven Gynecologic Malignancies. (PubMed, Int J Gynecol Pathol)
    On balance, our case exhibited morphologic and molecular features that overlap with (1) an undifferentiated uterine sarcoma, (2) an adenosarcoma with sarcomatous overgrowth, and (3) a mixed adenosarcoma and undifferentiated endometrial carcinoma. These hybrid features further expand the molecular-morphologic spectrum of SMARCA4/BRG1-deficient uterine neoplasms.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDK4 (Cyclin-dependent kinase 4) • KMT2C (Lysine Methyltransferase 2C) • ARID1B (AT-Rich Interaction Domain 1B) • NCOR1 (Nuclear Receptor Corepressor 1) • KAT6A (Lysine Acetyltransferase 6A) • SYP (Synaptophysin)
    |
    SMARCA4 mutation
    5ms
    Clear cell adenocarcinoma of Müllerian origin in a patient with germline SMARCA4 mutation. (PubMed, Int J Gynecol Cancer)
    No abstract available
    Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    SMARCA4 mutation
    5ms
    Evaluation of Efficacy and Prognosis Analysis of Stage III-IV SMARCA4-deficient Non-small Cell Lung Cancer Treated by PD-1 Immune Checkpoint Inhibitors plus Chemotherapy and Chemotherapy (PubMed, Zhongguo Fei Ai Za Zhi)
    Treatment regimen may be a prognostic factor for patients with SMARCA4-DNSCLC, and patients with PD-1 ICIs plus chemotherapy may have a better prognosis.
    Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    SMARCA4 mutation
    5ms
    Biomarkers-Based Cost-Effectiveness of Toripalimab Plus Chemotherapy for Patients with Treatment-Naive Advanced Non-Small Cell Lung Cancer. (PubMed, Adv Ther)
    From the perspective of the Chinese healthcare system, this study's findings suggested that first-line TC represents a cost-effective strategy for patients with advanced NSCLC. However, the cost-effectiveness of first-line TC varied across different subgroups when considering predictive biomarkers.
    Journal • HEOR • PD(L)-1 Biomarker • IO biomarker • Cost-effectiveness • Cost effectiveness • Metastases
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • RB1 (RB Transcriptional Corepressor 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    PD-L1 expression • EGFR mutation • ALK mutation • RB1 mutation • SMARCA4 mutation
    |
    Loqtorzi (toripalimab-tpzi) • toripalimab subcutaneous (JS001sc)
    6ms
    MYC overexpression and SMARCA4 loss cooperate to drive medulloblastoma formation in mice. (PubMed, Acta Neuropathol Commun)
    Finally, an integration of RNA sequencing and DNA methylation data of murine tumors with human samples revealed a high resemblance to human Group 3 medulloblastoma on the molecular level. Altogether, the development of SMARCA4-deficient medulloblastomas in mice paves the way to deciphering the role of frequently occurring SMARCA4 alterations in Group 3 medulloblastoma with the perspective to explore targeted therapeutic options.
    Preclinical • Journal
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    MYC overexpression • MYC expression • SMARCA4 mutation
    6ms
    Prognostic and predictive impact of molecular tumor burden index in non-small cell lung cancer patients. (PubMed, Thorac Cancer)
    ΔmTBI had a good sensitivity to identify potential beneficial patients based on the best effect CT scans, demonstrating that mTBI dynamics were predictive of benefit from immune checkpoint blockade.
    Journal • IO biomarker
    |
    RB1 (RB Transcriptional Corepressor 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    SMARCA4 mutation
    6ms
    Predicted Functional Consequences of TP53 Alterations and Prognosis in TP53-Mutated Mantle Cell Lymphoma (ASH 2023)
    The BOVEN trial aims to assess the efficacy of frontline treatment with zanubrutinib, obinutuzumab, and venetoclax in TP53mut MCL (Kumar Blood 2021). Across patients with TP53mut MCL treated either with standard frontline chemoimmunotherapy or on the BOVEN trial, predictions of intrinsic pathogenicity and functional consequences of the TP53 alterations were not prognostic. The impact of TP53 mutation VAF remains unclear, with seemingly opposite effect directions between the two cohorts, though neither finding was significant. As previously described in the comparator cohort, alterations in SMARCA4 are associated with worse PFS in TP53mut MCL, though this was not observed in the BOVEN cohort.
    Tumor mutational burden • IO biomarker
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ARID1A (AT-rich interaction domain 1A) • CCND1 (Cyclin D1) • KMT2D (Lysine Methyltransferase 2D) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • NOTCH2 (Notch 2) • ARID1B (AT-Rich Interaction Domain 1B)
    |
    TP53 mutation • ATM mutation • TP53 wild-type • ARID1A mutation • SMARCA4 mutation
    |
    Venclexta (venetoclax) • Gazyva (obinutuzumab) • Brukinsa (zanubrutinib)
    6ms
    The Efficacy of Obinutuzumab Combined with Pomalidomide and Covalent Btki for the Treatment of TP53 Mutated Mantle Cell Lymphoma (MCL): A Prospective, Open-Label, Single-Arm Study (ASH 2023)
    In this study, we investigated the application of Pomalidomide combined with Obinutuzumab and covalent BTKi (Ibrutinib and Zanubrutinib) for the treatment of TP53 mutated MCL to provide a new treatment evidence for clinical practice. The most common grade 3-4 adverse events were neutropenia (in 5 [35.7%] of 14 patients), thrombocytopenia (in 3 [21.4%] of 14 patients), infections (in 2[14.3%] patients), severe Covid-19 infection was in 2[14.3%] patients. Conclusions Our results provide preliminary evidence that the triplet combination of Obinutuzumab, pomalidomide, and covalent BTKi is an active regimen in MCL patients with the mutation of TP53, and should be evaluated in a prospective randomized controlled trial.
    Clinical
    |
    TP53 (Tumor protein P53) • CCND1 (Cyclin D1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    TP53 mutation • SMARCA4 mutation • CCND1 mutation
    |
    Imbruvica (ibrutinib) • Gazyva (obinutuzumab) • Brukinsa (zanubrutinib) • pomalidomide
    6ms
    Genomic and Transcriptomic Profiles of Blastoid and Pleomorphic Mantle Cell Lymphoma Are Distinct from Classic Histology Mantle Cell Lymphoma (ASH 2023)
    P and B-MCL have the highest degree of aneuploidy and exhibit an immune cold tumor microenvironment. Further studies are ongoing to refine the molecular differences among B and P-MCL compared to C-MCL.
    IO biomarker
    |
    TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • CCND1 (Cyclin D1) • BCL6 (B-cell CLL/lymphoma 6) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NOTCH2 (Notch 2) • CARD11 (Caspase Recruitment Domain Family Member 11) • MALT1 (MALT1 Paracaspase) • NFKBIE (NFKB Inhibitor Epsilon) • MIR15A (MicroRNA 15a)
    |
    TP53 mutation • ATM mutation • DNMT3A mutation • CDKN2A deletion • SMARCA4 mutation • CARD11 amplification • Chr del(13)(q14) • CCND1 mutation
    6ms
    Thoracic SMARCA4-Deficient Undifferentiated Tumors With Unusual Presentations: A Case Series. (PubMed, Int J Surg Pathol)
    Thoracic SMARCA4-UT should be considered in the differential diagnosis of pleomorphic rhabdoid tumors in older adults with a smoking history. Although most present as lung and/or mediastinal masses, they may occasionally present as a metastasis and mimic an undifferentiated sarcoma, representing a potential diagnostic pitfall.
    Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    SMARCA4 mutation
    6ms
    MULTIOMICS PROFILING OF CHINESE PATIENTS WITH SMALL CELL CARCINOMA OF THE OVARY, HYPERCALCEMIC TYPE (IGCS 2023)
    Among the 12 SCCOHT patients, 10 carried SMARCA4 mutations accompanied by loss of protein expression and 1 had a deletion of exon 1-6 in SMARCB1. Somatic variations affecting Notch and Hippo signaling pathway were detected in 60.0% of SCCOHT. Through gene set variation analysis (GSVA), the following pathways were up-regulated in SCCOHT compared with benign ovarian tissue: oxidative phosphorylation, MYC targets, E2F targets, G2M checkpoint, etc.
    Clinical
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1)
    |
    SMARCA4 mutation
    6ms
    METHYLATION PROFILING IDENTIFIES TWO DISTINCT CLUSTERS OF SMALL CELL CARCINOMA OF THE OVARY HYPERCALCEMIC TYPE (SCCOHT) (IGCS 2023)
    Our cohort included 27 SCCOHT. The age at diagnosis ranged from 7 – 47 years (n=25, median of 25 years) and 45 % of tumors where this information was available (n=20) presented with low stage disease. Clustering analysis of DNA methylation data identified two distinct tumor clusters (C1, n=15 and C2, n=12).
    IO biomarker
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    SMARCA4 mutation
    6ms
    The impact of genomic context on outcomes of solid cancer patients treated with genotype-matched targeted therapies: a comprehensive review. (PubMed, Ann Oncol)
    To our knowledge this is the most comprehensive review to date of the impact of genomic context on outcomes with targeted therapy. It represents a valuable resource informing progress towards contextualised precision medicine.
    Review • Journal • Tumor mutational burden
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    EGFR mutation • BRAF mutation • HER-2 amplification • HER-2 negative • MET amplification • TMB-L • ALK fusion • SMARCA4 mutation
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    Herceptin (trastuzumab) • Tagrisso (osimertinib) • Lumakras (sotorasib)
    6ms
    Disentangling the Joint and Distinct Immunomodulation and Vulnerability Between KEAP1/NFE2L2 and SMARCA4 Alterations in Lung Adenocarcinoma (ESMO-IO 2023)
    KEAP1/NFE2L2-MUT tumors showed various immunological abnormalities, highlighting the need for identifying targets to reinvigorate the immune response. SMARCA4-MUT tumors may be vulnerable to complement-targeted therapy.
    IO biomarker • Immunomodulating
    |
    EGFR (Epidermal growth factor receptor) • KEAP1 (Kelch Like ECH Associated Protein 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • AKR1C1 (Aldo-Keto Reductase Family 1 Member C1) • AKR1C2 (Aldo-Keto Reductase Family 1 Member C2)
    |
    EGFR mutation • KEAP1 mutation • SMARCA4 mutation • NFE2L2 mutation
    7ms
    A Study of Tazemetostat in Adult Participants With Soft Tissue Sarcoma (clinicaltrials.gov)
    P2, N=267, Active, not recruiting, Epizyme, Inc. | Trial completion date: Dec 2024 --> Jun 2024
    Trial completion date
    |
    CD34 (CD34 molecule) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
    |
    SMARCA4 mutation
    |
    Tazverik (tazemetostat)
    8ms
    SMARCA4 (BRG-1)–Deficient Dedifferentiated Ovarian Carcinoma Mimicking Mixed Germ Cell Tumor in a Young Woman: A Diagnostic Pitfall (CAP 2023)
    SALL-4 reactivity, generally considered specific for germ cell tumors, is indicative of stem cell–like differentiation in poorly differentiated somatic cancers. A high index of suspicion, thorough sampling, and mutational profiling using NGS can improve diagnostic accuracy.
    Clinical
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • GPC3 (Glypican 3)
    |
    SMARCA4 mutation
    8ms
    Defining the first bona fide cell model for SMARCA4-deficient, undifferentiated tumor. (PubMed, J Pathol)
    © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland
    Journal
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    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CD34 (CD34 molecule) • SOX2 • SALL4 (Spalt Like Transcription Factor 4) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
    |
    SMARCA4 mutation
    9ms
    Esophageal carcinoma with SMARCA4 mutation: Unique diagnostic challenges. (PubMed, Pathol Res Pract)
    Two of the patients deceased 72 and 78 days after diagnosis, and the other two patients showed limited or no treatment response to chemotherapy. In conclusion, esophageal carcinoma with SMARCA4 mutation may pose significant diagnostic challenge for surgical pathologists due to its variable morphology and immunoprofile, and accurate classification of this entity requires recognition of the spectrum of morphology and utilization of BRG1 immunostain and next generating sequencing.
    Journal
    |
    TP53 (Tumor protein P53) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    TP53 mutation • SMARCA4 mutation • SMARCA4 deletion
    9ms
    To be, or not to be: the dilemma of immunotherapy for non-small cell lung cancer harboring various driver mutations. (PubMed, J Cancer Res Clin Oncol)
    Many gene mutations have been shown to be associated with immunotherapy efficacy. Gene mutations should be combined with PD-L1, TMB, etc. to predict the effect of immunotherapy.
    Review • Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • EML4 (EMAP Like 4) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • PBRM1 (Polybromo 1) • LRP1B (LDL Receptor Related Protein 1B) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • FAT3 (FAT Atypical Cadherin 3) • ZFHX3 (Zinc Finger Homeobox 3) • EPHA5 (EPH Receptor A5)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • EGFR mutation • TMB-H • PIK3CA mutation • MET exon 14 mutation • ALK mutation • KEAP1 mutation • PBRM1 mutation • MET mutation • SMARCA4 mutation
    9ms
    Phase 1 Study of the Dual MDM2/MDMX Inhibitor ALRN-6924 in Pediatric Cancer (clinicaltrials.gov)
    P1, N=21, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed | N=69 --> 21
    Trial completion • Enrollment change
    |
    TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase) • TET2 (Tet Methylcytosine Dioxygenase 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D)
    |
    TP53 wild-type • MDM2 amplification • TET2 mutation • SMARCA4 mutation • PPM1D mutation
    |
    cytarabine • ALRN-6924