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    BIOMARKER:

    IKZF1 deletion + PAX5 deletion

    i
    Other names: IKZF1, IKAROS Family Zinc Finger 1, Zinc Finger Protein Subfamily 1A 1 (Ikaros), Protein Phosphatase 1 Regulatory Subunit 92, Ikaros Family Zinc Finger Protein 1, Lymphoid Transcription Factor LyF-1, DNA-Binding Protein Ikaros, ZNFN1A1, IKAROS, LYF1, IK1, IKAROS Family Zinc Finger 1 (Ikaros), CLL-Associated Antigen KW-6, Hs.54452, PPP1R92, PRO0758, CVID13, LyF-1, PAX5, Paired Box 5, B-Cell Lineage Specific Activator, BSAP, Paired Box Gene 5, B-Cell-Specific Transcription Factor, Paired Box Homeo
    Entrez ID:
    10320; 5079
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    over3years
    Genetic and epigenetic landscape of IDH-wildtype glioblastomas with FGFR3-TACC3 fusions. (PubMed, Acta Neuropathol Commun)
    Despite being older at diagnosis and having similar frequencies of MGMT promoter hypermethylation, patients with F3T3-positive GBMs lived about 8 months longer than those with F3T3-wildtype tumors. While consistent with IDH-wildtype GBM, F3T3-positive GBMs exhibit distinct biological features, underscoring the importance of pursuing molecular studies prior to clinical trial enrollment and targeted treatment.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3)
    |
    EGFR amplification • FGFR3-TACC3 fusion • FGFR3 fusion • IKZF1 deletion + PAX5 deletion
    over3years
    Recurrent urothelial carcinoma-like FGFR3 genomic alterations in malignant Brenner tumors of the ovary. (PubMed, Mod Pathol)
    Finally, malignant Brenner tumors had overall distinct genomic signatures compared to FGFR-mutated ovarian serous, endometrioid, and clear cell carcinoma subtypes. This study provides insights into the molecular pathogenesis of malignant Brenner tumors, contrasts the extent of FGFR1/2/3 alterations in ovarian serous, clear cell and endometrioid carcinomas and emphasizes the potential value of novel and FDA-approved, anti-FGFR inhibitors, such as erdafitinib and pemigatinib, in refractory, FGFR3-mutated malignant Brenner tumors.
    Journal • Tumor Mutational Burden
    |
    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TACC3 (Transforming acidic coiled-coil containing protein 3) • MDM2 (E3 ubiquitin protein ligase)
    |
    TP53 mutation • PIK3CA mutation • HRD • FGFR1 amplification • TMB-L • FGFR2 amplification • FGFR3 mutation • MDM2 amplification • FGFR3 S249C • PIK3CA amplification • FGFR3 fusion • MDM2 mutation • FGFR3 amplification • IKZF1 deletion + PAX5 deletion
    |
    Balversa (erdafitinib) • Pemazyre (pemigatinib)
    over3years
    [VIRTUAL] DEBIO1347, AN ORAL FGFR INHIBITOR: RESULTS FROM A SINGLE CENTER STUDY IN RECURRENT/REFRACTORY FGFR ALTERED PEDIATRIC GLIOMAS (SIOP 2020)
    Conclusions Debio1347 demonstrated tolerable toxicity and promising anti-tumor efficacy in pediatric patients with refractory FGFR altered gliomas. Further studies in this population are warranted.
    Clinical
    |
    FGFR3 (Fibroblast growth factor receptor 3) • FGFR (Fibroblast Growth Factor Receptor) • TACC3 (Transforming acidic coiled-coil containing protein 3)
    |
    FGFR3 mutation • FGFR1 mutation • FGFR1 fusion • FGFR3 fusion • IKZF1 deletion + PAX5 deletion
    |
    zoligratinib (Debio 1347)
    almost4years
    [VIRTUAL] Oncogenic fusions in CNS gliomas assessed by next generation sequencing: The real-world experience (ESMO 2020)
    Legal entity responsible for the study: The authors. Funding: Supported by Charles University Research Fund (Progres Q39) and MH CZ-DRO (University Hospital Plzen-FNPl, 00669806).
    Clinical • Real-World Evidence • Next-generation sequencing
    |
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • TACC3 (Transforming acidic coiled-coil containing protein 3) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • KIAA1549 • EWSR1 (EWS RNA Binding Protein 1)
    |
    ALK rearrangement • FGFR2 fusion • ALK fusion • FGFR fusion • KIAA1549-BRAF fusion • BRAF fusion • FGFR1 fusion • MET fusion • IKZF1 deletion + PAX5 deletion • KIT fusion
    almost4years
    [VIRTUAL] Genomic aberration of FGF/FGFR and genes related to primary resistance to FGFR inhibitor in urothelial carcinoma (AUA 2020)
    The incidence of genomic FGF/FGFR aberration in urothelial carcinoma is approximately 41.0%. Of which, the frequency of genetic alteration related to resistance to FGFR inhibitor is practically 53.0%, including KRAS (6%), ERBB2 (12%), PIK3CA (14%) and TSC1 (10%). Source of Funding: No
    Tumor Mutational Burden • MSi-H Biomarker • 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) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • TACC3 (Transforming acidic coiled-coil containing protein 3) • FGFR4 (Fibroblast growth factor receptor 4) • TSC1 (TSC complex subunit 1) • FGF (Fibroblast Growth Factor)
    |
    FGFR3 mutation • FGFR mutation • FGFR3 fusion • IKZF1 deletion + PAX5 deletion
    4years
    [VIRTUAL] A novel xenonucleic acid-mediated fusion gene detection method for cancer diagnostic (AACR-II 2020)
    XNA can effectively suppress the amplification from WT RNA transcript and enhances fusion transcripts detection during target sequencing. TACC3 XNA successfully increased fusion read percentage from 2.68% to 60.12%. More studies are being conducted to evaluate the effectiveness of XNA on other fusions.
    Late-breaking abstract
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • FGFR3 (Fibroblast growth factor receptor 3) • EML4 (EMAP Like 4) • CD74 (CD74 Molecule) • TACC3 (Transforming acidic coiled-coil containing protein 3) • TPM3 (Tropomyosin 3)
    |
    NTRK1 fusion • EML4-ALK fusion • ALK fusion • ROS1 fusion • FGFR3 fusion • FGFR3 amplification • IKZF1 deletion + PAX5 deletion
    4years
    [VIRTUAL] Characterization of multiple driver alterations in acquired resistance to osimertinib in EGFR-mutated lung cancer: implementation of single cell approaches (AACR-II 2020)
    Combining targeted therapies represents a valuable therapeutic opportunity to overcome drug resistance in EGFR-mutated lung cancer. Updated results will be presented at the Meeting.
    Preclinical • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3) • STRN (Striatin)
    |
    BRAF V600E • EGFR mutation • BRAF V600 • EGFR L858R • EGFR exon 19 deletion • RET fusion • ALK fusion • FGFR3 mutation • FGFR3 fusion • STRN-ALK fusion • EGFR L858R + EGFR exon 19 deletion • IKZF1 deletion + PAX5 deletion
    |
    Tagrisso (osimertinib)
    4years
    [VIRTUAL] MSK-ACCESS for the detection of fibroblast growth factor receptor-3 (FGFR3) mutations in plasma cell-free (cf)DNA of metastatic urothelial carcinoma (mUC) patients (pts) pre- and on erdafitinib (erda) therapy. (ASCO 2020)
    A high degree of concordance between primary tumor and cfDNA FGFR3 mutation detection was observed. FGFR3 mutations exclusive to cfDNA were found in a subset of pts. Further pt accrual and follow-up are ongoing to assess for correlations between erda response and tx-related changes in cfDNA MAF, and to assess whether cfDNA can identify resistance mechanisms.
    Clinical
    |
    FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR (Fibroblast Growth Factor Receptor) • TACC3 (Transforming acidic coiled-coil containing protein 3) • FGF (Fibroblast Growth Factor)
    |
    FGFR2 mutation • FGFR3 mutation • FGFR3 S249C • FGFR3 Y373C • FGFR3 fusion • FGFR3 R248C • IKZF1 deletion + PAX5 deletion
    |
    Balversa (erdafitinib)
    4years
    [VIRTUAL] Final results from the phase I study expansion cohort of the selective FGFR inhibitor Debio 1,347 in patients with solid tumors harboring an FGFR gene fusion. (ASCO 2020)
    Debio 1347 at the recommended dose of 80 mg qd was generally well tolerated and showed signs of activity in solid tumors harboring an FGFR fusion. The FUZE phase 2 clinical trial of Debio 1347 is recruiting FGFR fusion-positive advanced solid tumors irrespectively of tumor histology, excluding PBT. Research Funding: Debiopharm International SA
    Clinical • P1 data
    |
    FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3)
    |
    FGFR2 fusion • FGFR1 fusion • IKZF1 deletion + PAX5 deletion
    |
    zoligratinib (Debio 1347)
    4years
    Absence of FGFR3-TACC3 rearrangement in hematological malignancies with numerical chromosomal alteration. (PubMed, Hematol Oncol Stem Cell Ther)
    Because chromosome numerical alterations, hallmarks of FGFR-TACC fusions are present in many hematological disorders and there are no data on the prevalence, we studied a series of patients with acute myeloid leukemia and myelodysplastic syndrome who presented numerical alterations using cytogenetic traditional analysis. None of the analyzed samples showed FGFR3-TACC3 gene fusion, so screening for this mutation at diagnosis is not recommended.
    Journal
    |
    FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3)
    |
    FGFR3 mutation • IKZF1 deletion + PAX5 deletion