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    GENE:

    CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2)

    i
    Other names: CAPZA2, Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2, CAPPA2, CAPZ, Capping Protein (Actin Filament) Muscle Z-Line, Alpha 2, Capping Actin Protein Of Muscle Z-Line Alpha Subunit 2, F-Actin Capping Protein Alpha-2 Subunit, F-Actin-Capping Protein Subunit Alpha-2, CapZ Alpha-2. Epididymis Secretory Sperm Binding Protein
    5ms
    A subgroup of anaplastic thyroid carcinomas harbors MET alterations with potential therapeutic options. (PubMed, Pathol Res Pract)
    As these alterations are druggable in other cancers, early molecular testing may identify MET-positive ATCs eligible for anti-MET therapies in clinical trials. We recommend RNA-based sequencing and FISH as biomarker assays to identify MET alterations.
    Journal
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    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • TERT (Telomerase Reverse Transcriptase) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase) • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2)
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    TP53 mutation • BRAF V600E • PIK3CA mutation • BRAF V600 • MET amplification • MET exon 14 mutation • MET overexpression • RAS mutation • MET mutation • MET positive
    over1year
    Fusion transcriptome landscape in Glioblastoma (SNO 2024)
    Comprehensive molecular profiling reveals that approximately 10% of IDH WT GBMs carry oncogenic fusions that may be therapeutic targets. Broad spectrum of observed fusions underscores the need for novel clinical trial designs to allow efficient enrollment for prospective testing of potential targeted agents.
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CDK4 (Cyclin-dependent kinase 4) • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • SEC61G (SEC61 Translocon Subunit Gamma) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)
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    TP53 mutation • EGFR mutation • NTRK1 fusion • NTRK2 fusion • MET amplification • EGFR amplification • ALK fusion • ROS1 fusion • MET mutation • EGFRvIII mutation • FGFR3 fusion • IDH wild-type • EGFR fusion
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    MI Tumor Seek™
    over1year
    HIGH FREQUENCIES OF FUSION TRANSCRIPTS (FT) IDENTIFIED IN OVARIAN CLEAR CELL CARCINOMA (OCCC) BY COMPREHENSIVE GENOMIC PROFILING (CGP) (IGCS 2024)
    Conclusion/Implications Early-stage OCCC tumors showed high occurence of FT associated with lower immune scores and recurrence rate. Functional elucidation of novel FT is warranted.
    Tumor mutational burden
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    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2)
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    TMB-H • TMB-L
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    TruSight Oncology 500 Assay • TruSight Oncology 500 HRD Assay
    2years
    Comprehensive clinicopathological, molecular, and methylation analysis of mesenchymal tumors with NTRK and other kinase gene aberrations. (PubMed, J Pathol)
    © 2024 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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    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CD34 (CD34 molecule) • NTRK (Neurotrophic receptor tyrosine kinase) • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • WWP2 (WW Domain Containing E3 Ubiquitin Protein Ligase 2)
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    EGFR mutation • BRAF mutation • MET fusion • BRAF mutation + EGFR mutation
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    Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Retevmo (selpercatinib)
    2years
    SEPTIN10-mediated crosstalk between cytoskeletal networks controls mechanotransduction and oncogenic YAP/TAZ signaling. (PubMed, Cancer Lett)
    Importantly, the crosstalk between microfilaments and microtubules is mediated by SEPTIN10 as its loss abrogates actin stress fiber formation after microtubule disruption. Together, the YAP/TAZ target gene SEPTIN10 controls the dynamic interplay between actin and microtubule filaments, which feeds back on Hippo pathway activity in HCC cells and thus acts as molecular switch with impact on oncogenic signaling and cancer cell biology.
    Journal
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    CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • SEPTIN10 (Septin 10) • TAFAZZIN (Tafazzin)
    over2years
    Pan-cancer prevalence of MET fusions and clinical response to MET- targeted therapy (ESMO 2023)
    Treatment with type 2 (cabozantinib) or type 1 (crizotinib, capmatinib, savolitinib) MET TKIs blocked growth of SJ-GBM2 cells with IC50 values of 0.3, 0.2, 0.1 and 0.04 μM, respectively, reflecting the sensitivity observed in H1993 and EBC1...Conclusions Our findings indicate MET fusions are widely distributed among tumor types and are sensitive to type 1 and type 2 MET TKIs. Clinical trials evaluating MET inhibitors for patients whose cancers are driven by MET fusions are ongoing.
    Clinical • Pan tumor
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    CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • NRG2 (Neuregulin 2) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1) • ZKSCAN1 (Zinc Finger With KRAB And SCAN Domains 1)
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    MET amplification • MET expression • MET fusion
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    Xalkori (crizotinib) • Cabometyx (cabozantinib tablet) • Orpathys (savolitinib) • Tabrecta (capmatinib)
    over2years
    Molecular Characteristics of Non-Small Cell Lung Cancer with MET Fusions (IASLC-WCLC 2023)
    MET fusions are a rare, but potentially actionable, genomic alteration. Our study provides a comprehensive characterization of MET fusions in NSCLC, revealing their diverse fusion partners and co-occurring genomic alterations. Further research is warranted to elucidate the clinical implications of MET fusions in the treatment of various types of cancer, including lung cancer.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • KIF5B (Kinesin Family Member 5B) • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • GPRC5C (G Protein-Coupled Receptor Class C Group 5 Member C)
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    PD-L1 expression • BRAF V600E • KRAS mutation • EGFR mutation • TMB-H • PD-L1 overexpression • BRAF V600 • EGFR L858R • MET amplification • RET fusion • MET exon 14 mutation • EGFR mutation + KRAS mutation • BRAF L597Q • MET fusion • EGFR E746 • KRAS Q61L • PD-L1-L • BRAF L597
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    PD-L1 IHC 22C3 pharmDx • FusionPlex® Dx • MI Tumor Seek™
    over2years
    Brief Report: MET fusions in Non-small cell lung cancer: Clinicopathologic features and response to MET inhibition. (PubMed, J Thorac Oncol)
    MET fusions are very rare oncogenic driver events in NSCLC and predominantly appear in adenocarcinomas. They are heterogeneous in terms of fusion partners and breakpoints. Patients with MET fusion can benefit from MET TKI therapy.
    Journal
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    BRAF (B-raf proto-oncogene) • KIF5B (Kinesin Family Member 5B) • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • PRKAR1A (Protein Kinase CAMP-Dependent Type I Regulatory Subunit Alpha) • TRIM4 (Tripartite Motif Containing 4) • PRKAR2B (Protein Kinase CAMP-Dependent Type II Regulatory Subunit Beta)
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    BRAF V600E • BRAF V600 • MET mutation • MET fusion
    over2years
    Fusion Detection in Primary Neoplasms of the CNS Using the TSO500 NGS RNA/DNA Hybrid Panel (AANP 2023)
    In addition to common partners (e.g. KIAA1549 for BRAF) we detected less common partners to BRAF including GTF21 as well as less common partners for MET and NTRK2 fusions in glioma. Future studies are needed to determine the full diagnostic utility and therapeutic implications of expanded fusion detection.
    Next-generation sequencing
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    BRAF (B-raf proto-oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • TACC3 (Transforming acidic coiled-coil containing protein 3) • KIAA1549 • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • SHTN1 (Shootin 1) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)
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    NTRK2 fusion • FGFR2 fusion • KIAA1549-BRAF fusion • FGFR1 fusion • FGFR3 fusion • QKI-RAF1 fusion
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    TruSight Oncology 500 Assay
    3years
    Investigation of M2 macrophage-related gene affecting patients prognosis and drug sensitivity in non-small cell lung cancer: Evidence from bioinformatic and experiments. (PubMed, Front Oncol)
    Meanwhile, the estimated IC50 of seven drugs differs significantly between two risk groups, including Cisplatin, Docetaxel, Doxorubicin, Gefitinib, Paclitaxel, Sunitinib and Vinorelbine. In summary, our study identified the molecules significantly affecting M2 macrophage infiltration and identified a prognosis signature that robustly indicated patients prognosis. Moreover, we validated the cancer-promoting effect of HNMT using in vitro experiments.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • HS3ST2 (Heparan Sulfate-Glucosamine 3-Sulfotransferase 2) • TM6SF1 (Transmembrane 6 Superfamily Member 1)
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    cisplatin • gefitinib • paclitaxel • docetaxel • sunitinib • doxorubicin hydrochloride • vinorelbine tartrate
    3years
    MET gene alterations predict poor survival following chemotherapy in patients with advanced cancer. (PubMed, Pathol Oncol Res)
    Thus, MET aberration was determined to be a factor of response to chemotherapy. Approximately 2.1% and 0.4% of patients with advanced solid tumors demonstrated MET gene amplification and fusion, respectively, and displayed a worse response to chemotherapy and significantly shorter OS and PFS than those without MET gene amplification or fusion.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • MSI (Microsatellite instability) • CAV1 (Caveolin 1) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • PCM1 (Pericentriolar Material 1) • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2)
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    TMB-H • MET amplification • MET mutation • MET positive • MET fusion
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    PD-L1 IHC 22C3 pharmDx
    over3years
    Retrospective review of glioma patients with confirmed MET amplification or fusion (SNO 2022)
    MET amplification and fusion alterations were observed in both low and high grade gliomas, suggesting that they may be involved in early tumorigenesis. Survival outcomes were poor compared with historical data, with no differences observed between treatment groups, suggesting that current therapeutic modalities may be inadequate. This study indicates that MET may be an appropriate therapeutic target, laying the groundwork for clinical trials investigating MET-targeted agents.
    Retrospective data • Review
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    MET (MET proto-oncogene, receptor tyrosine kinase) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MGMT (6-O-methylguanine-DNA methyltransferase) • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)
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    MET amplification • IDH wild-type • MET fusion