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    BIOMARKER:

    MDM2 amplification

    i
    Other names: MDM2, HDM2, MGC5370, MDM2 proto-oncogene, E3 ubiquitin protein ligase
    Entrez ID:
    4193
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    11ms
    Brightline-2: A Study to Test Whether Brigimadlin (BI 907828) Helps People With Cancer in the Biliary Tract, Pancreas, Lung or Bladder (clinicaltrials.gov)
    P2, N=99, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Nov 2026 --> Jun 2025 | Trial primary completion date: Feb 2025 --> Jun 2025
    Trial completion date • Trial primary completion date
    |
    TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)
    |
    TP53 wild-type • MDM2 amplification
    |
    brigimadlin (BI 907828)
    11ms
    Genomic profiling of intimal sarcoma reveals molecular subtypes with distinct tumor microenvironments and therapeutic implications. (PubMed, ESMO Open)
    We identified two intimal sarcoma molecular subtypes. Compared with CNV-H, MSI-H-like is enriched in pathways associated with tumor immune responses and TILs. Further efforts and clinical trials to better define these molecular subtypes are warranted to open new avenues for personalized treatment approaches and improve patient outcomes.
    Journal • MSi-H Biomarker • PD(L)-1 Biomarker
    |
    MSI (Microsatellite instability) • MDM2 (E3 ubiquitin protein ligase) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • MLH1 (MutL homolog 1) • CDK4 (Cyclin-dependent kinase 4) • TNFA (Tumor Necrosis Factor-Alpha)
    |
    MSI-H/dMMR • MDM2 amplification • CDK4 amplification • MLH1 mutation
    |
    Keytruda (pembrolizumab)
    11ms
    Study of ASTX295 in Patients With Solid Tumors With Wild-Type p53 (clinicaltrials.gov)
    P1/2, N=106, Terminated, Taiho Oncology, Inc. | Trial completion date: Jun 2025 --> Aug 2024 | Active, not recruiting --> Terminated; Sponsor Decision
    Trial completion date • Trial termination
    |
    TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)
    |
    TP53 wild-type • MDM2 amplification
    |
    ASTX295
    11ms
    Molecular diversity of embryonic-type neuroectodermal tumors arising from testicular germ cell tumors. (PubMed, Mod Pathol)
    In summary, ENTs arising from GCTs are molecularly heterogeneous; however, a large fraction of testicular ENTs could be stratified by two distinct sets of genetic alterations, including MYCN/MYC amplification with concurrent suppression of the p53 pathway, and activation of the PI3K pathway with co-occurring CDK4 amplification. Moreover, the novel gene fusions identified in a subset of testicular GCT-derived ENTs overlap with molecularly defined tumors of embryonic-type neuroectodermal features in the central nervous system, indicating the potential common driving events for tumorigenesis from different anatomic sites.
    Journal • Tumor mutational burden
    |
    KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MDM2 (E3 ubiquitin protein ligase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler) • BCOR (BCL6 Corepressor) • PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma) • CCND2 (Cyclin D2) • BRD4 (Bromodomain Containing 4) • PIK3C2B (Phosphatidylinositol-4-Phosphate 3-Kinase Catalytic Subunit Type 2 Beta)
    |
    TP53 mutation • PIK3CA mutation • TMB-L • MDM2 amplification • CDK4 amplification • MDM2 mutation • PIK3CB mutation
    11ms
    This Study Aims to Find the Best Dose of BI 907828 (Brigimadlin) in Patients With Different Types of Advanced Cancer (Solid Tumors) (clinicaltrials.gov)
    P1, N=267, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Apr 2026 --> Jun 2025 | Trial primary completion date: Mar 2026 --> Jun 2025
    Trial completion date • Trial primary completion date
    |
    TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)
    |
    TP53 wild-type • MDM2 amplification
    |
    brigimadlin (BI 907828)
    1year
    Brightline-2: A Study to Test Whether Brigimadlin (BI 907828) Helps People With Cancer in the Biliary Tract, Pancreas, Lung or Bladder (clinicaltrials.gov)
    P2, N=100, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)
    |
    TP53 wild-type • MDM2 amplification
    |
    brigimadlin (BI 907828)
    1year
    Overdiagnosis of atypical lipomatous tumors/well-differentiated liposarcomas by morphological diagnosis using only HE stained specimens: a case-control study with MDM2/CDK4 immunostaining and MDM2/CDK4 fluorescence in situ hybridization. (PubMed, BMC Cancer)
    Morphological diagnosis alone can accurately diagnose lipomas. However, it has a propensity to overdiagnose ALT/WDLPS. Thus, MDM2 FISH should be used more proactively, not only for lesions with obvious morphological abnormalities, but also for lipomatous tumors that are clinically suggestive of ALT/WDLPS.
    Journal
    |
    MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
    |
    MDM2 amplification • CDK4 amplification
    1year
    Low-Level MDM2 Amplification by FISH: An Institutional Experience With a Diagnostic Dilemma. (PubMed, Int J Surg Pathol)
    Laboratory measures and utilizing NGS assay when needed, could be implemented when encountering such problematic "low-level" MDM2 amplification specimens to avoid misdiagnosis and misuse of targeted therapy. Future studies are needed to better characterize and investigate such findings.
    Journal
    |
    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MDM2 (E3 ubiquitin protein ligase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    MDM2 amplification
    1year
    Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (AIOM 2024)
    4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.
    Clinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • PIK3CA mutation • MET amplification • ALK rearrangement • FGFR1 amplification • POLE mutation • NF1 mutation • MDM2 amplification • RET mutation • PTCH1 mutation • NF2 mutation • ROS1 mutation • BRCA mutation • ALK rearrangement + PIK3CA mutation • PTCH1 rearrangement • NTRK fusion
    |
    FoundationOne® CDx
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)
    1year
    Therapy-relevant MDM2 amplification in cholangiocarcinomas in Caucasian patients. (PubMed, Ther Adv Med Oncol)
    Real-world evidence in our Caucasian patient population confirmed that a significant number of intrahepatic CCAs showcase MDM2 amplification, qualifying for a personalized therapy option with Brigimadlin. MDM2 amplification must therefore be considered in the context of personalized molecular testing in CCA.
    Journal
    |
    FGFR2 (Fibroblast growth factor receptor 2) • MDM2 (E3 ubiquitin protein ligase)
    |
    TP53 wild-type • MDM2 amplification
    |
    brigimadlin (BI 907828)
    1year
    Primary Liposarcoma of the Spleen: Case Report With Review of the Literature. (PubMed, Int J Surg Pathol)
    To the best of our knowledge, this is the first description of a primary liposarcoma of the spleen reported in the literature. Due to the local recurrence risk of liposarcomas, even after R0 resection, we recommended long-term periodic follow-up.
    Review • Journal
    |
    MDM2 (E3 ubiquitin protein ligase)
    |
    MDM2 amplification
    1year
    Primary intracranial dedifferentiated liposarcoma: An extremely rare site with unusual histopathological findings. (PubMed, Neuropathology)
    Final diagnosis of DDLS was rendered. The patient had no systemic lesions elsewhere on positron emission tomography computed tomography scan.
    Journal
    |
    MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • GFAP (Glial Fibrillary Acidic Protein) • OLIG2 (Oligodendrocyte Transcription Factor 2)
    |
    MDM2 amplification