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    BIOMARKER:

    MDM2 amplification + CDK4 amplification

    i
    Other names: MDM2, HDM2, MGC5370, MDM2 proto-oncogene, E3 ubiquitin protein ligase, CDK4, PSK-J3, Cyclin-dependent kinase 4
    Entrez ID:
    4193; 1019
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    2ms
    Well-differentiated liposarcomas and dedifferentiated liposarcomas: Systemic treatment options for two sibling neoplasms. (PubMed, Cancer Treat Rev)
    Several regimens have been tested with modest results regarding their efficacy. Herein we discuss the systemic treatment options for WDLPS and DDLPS and review their reported clinical efficacy results.
    Review • Journal
    |
    MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
    |
    MDM2 amplification + CDK4 amplification
    3ms
    CDK4/MDM2 Amplification Is a Rare Targetable Genomic Event in TP53/RB1-Wildtype Uterine Leiomyosarcoma (USCAP 2024)
    Overall, in our uLMS analysis, CDK4 and/or MDM2 amplification was identified in a small subset (2%) of uLMS, the majority of which are TP53/RB1-wildtype. This may suggest that CDK4/MDM2 amplification can be an alternative tumorigenic mechanism in this distinct class of uLMS, which may have therapeutic clinical implications, including possible use of specific cyclin-dependent kinase inhibitors.
    Tumor mutational burden
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler)
    |
    TP53 mutation • MDM2 amplification • CDK4 amplification • MDM2 amplification + CDK4 amplification • RB1 wild-type • CDK4 mutation
    |
    FoundationOne® Heme CDx
    3ms
    CDK4/MDM2 Amplification Is a Rare Targetable Genomic Event in TP53/RB1-Wildtype Uterine Leiomyosarcoma (USCAP 2024)
    Overall, in our uLMS analysis, CDK4 and/or MDM2 amplification was identified in a small subset (2%) of uLMS, the majority of which are TP53/RB1-wildtype. This may suggest that CDK4/MDM2 amplification can be an alternative tumorigenic mechanism in this distinct class of uLMS, which may have therapeutic clinical implications, including possible use of specific cyclin-dependent kinase inhibitors.
    Tumor mutational burden
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler)
    |
    TP53 mutation • MDM2 amplification • CDK4 amplification • MDM2 amplification + CDK4 amplification • RB1 wild-type • CDK4 mutation
    |
    FoundationOne® Heme CDx
    4ms
    Soft Tissue Sarcomas with Chromosomal Alterations in the 12q13-15 Region: Differential Diagnosis and Therapeutic Implications. (PubMed, Cancers (Basel))
    This suggests the potential use of MDM2 or CDK4 inhibitors in neoplasms where alterations in these genes do not aid the pathological diagnosis but may help identify potential therapeutic targets. In this review, we delve into the diagnosis and therapeutic implications of tumors with genetic alterations involving the chromosomal region 12q13-15, mainly MDM2, CDK4, and GLI1.
    Review • Journal
    |
    MDM2 (E3 ubiquitin protein ligase) • GLI1 (GLI Family Zinc Finger 1) • STAT6 (Signal transducer and activator of transcription 6) • DDIT3 (DNA-damage-inducible transcript 3)
    |
    CDK4 amplification • MDM2 amplification + CDK4 amplification
    7ms
    Liposarcoma Involving Serous Fluid Cavities-A Case Series Illustrating Clinical Implications and the Diagnostic Role of Exfoliative Cytology. (PubMed, Int J Surg Pathol)
    Lipomatous and dedifferentiated components can be sampled and cytomorphologically identified on effusion fluids of liposarcomas, with sufficient cellularity for immunocytochemistry and molecular testing. Although generally associated with poor prognosis, long disease-free survival with sarcomatous effusion is possible with radical surgery and adjuvant treatment.
    Journal • Cytology
    |
    MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
    |
    MDM2 amplification • CDK4 amplification • MDM2 amplification + CDK4 amplification
    10ms
    Endometrial stromal sarcomas with BCOR alterations: clinicopathological and molecular study of a rare subgroup (ECP 2023)
    We also detected a subset of cases with MDM2 and CDK4 amplification, along with CDKN2A and/or RB1 deletion. This emphasizes the clinical relevance of detailed molecular characterization of BCOR-associated ESS to identify potential candidates to CDK4/6 inhibitors.
    Clinical • Stroma
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • MDM2 (E3 ubiquitin protein ligase) • BCOR (BCL6 Corepressor) • MME (Membrane Metalloendopeptidase) • JAZF1 (JAZF Zinc Finger 1)
    |
    CDKN2A deletion • RB1 deletion • CDK4 amplification • CCND1 expression • MDM2 amplification + CDK4 amplification • RB deletion
    11ms
    New targeted treatments for advanced sarcomas. (PubMed, Curr Opin Oncol)
    Molecular-guided precision medicine holds a bright future in bringing more active treatments for advanced sarcoma patients.
    Journal • IO biomarker • Metastases
    |
    MDM2 (E3 ubiquitin protein ligase) • XPO1 (Exportin 1) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
    |
    CDK4 amplification • MDM2 overexpression • MDM2 amplification + CDK4 amplification • SS18-SSX fusion
    |
    imatinib • Xpovio (selinexor) • Tazverik (tazemetostat) • milademetan (RAIN-32) • Fyarro (nanoparticle albumin-bound rapamycin) • brigimadlin (BI 907828)
    1year
    Intra-Abdominal and Retroperitoneal Benign Lipomatous Tumors-An Extremely Rare Mimic of Liposarcoma and its Diagnostic Challenge. (PubMed, Int J Surg Pathol)
    This necessitates molecular confirmation even when the histology is convincingly benign, for a confident diagnosis. Our cohort shows that conservative excision without removal of abutted organs is sufficient in most cases.
    Journal
    |
    MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • MME (Membrane Metalloendopeptidase)
    |
    CDK4 amplification • MDM2 amplification + CDK4 amplification
    1year
    Anisometric Cell/Dysplastic Lipomas in a Retinoblastoma Survivor: Report of a Case with Review of the Literature. (PubMed, Int J Surg Pathol)
    AC/DLs in RB survivors are characterized by multiplicity, unifying histology, and benign course. Their biology appears distinct from ordinary lipomas, spindle cell lipomas, and atypical lipomatous tumors.
    Review • Journal
    |
    RB1 (RB Transcriptional Corepressor 1) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
    |
    RB1 deletion • MDM2 amplification + CDK4 amplification
    over1year
    The Landscape of Somatically Actionable Genes Identified by DNA-NGS in Chinese Melanoma Patients (AMP 2022)
    In summary, we present the druggable mutation landscape of 469 Chinese melanoma patients, and our work provides a workable translational genome-driven precision oncology strategy in melanoma patients, demonstrating the potential of individualized treatment for this rare but intractable disease.
    Clinical • Tumor mutational burden • MSi-H Biomarker • Next-generation sequencing
    |
    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • NF1 (Neurofibromin 1) • NRG1 (Neuregulin 1) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
    |
    TMB-H • MSI-H/dMMR • BRAF mutation • NRAS mutation • NF1 mutation • MDM2 amplification • NRG1 fusion • BRAF fusion • CDK4 amplification • MDM2 amplification + CDK4 amplification
    |
    Onco PanScan™
    over1year
    Giant Paratesticular Liposarcoma: Molecular Characterization and Management Principles with a Review of the Literature. (PubMed, Diagnostics (Basel))
    In conclusion, the presence of a liposarcoma should be taken into account during the diagnostic workup of scrotal masses, in order to minimize the rate of misdiagnosis and improper management. Molecular analysis may support histological characterization of these rare entities and potentially disclose novel therapeutic targets.
    Review • Journal
    |
    MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
    |
    MDM2 amplification + CDK4 amplification
    almost2years
    Amplification of CDK4 and MDM2: a detailed study of a high-risk neuroblastoma subgroup. (PubMed, Sci Rep)
    Pharmacological inhibition of CDK4/6 with ribociclib or abemaciclib decreased proliferation in a broad set of neuroblastoma cell lines, including CDK4/MDM2-amplified, whereas MDM2 inhibition by Nutlin-3a was only effective in p53 cells. An atypical metastatic pattern was also observed with low degree of bone marrow involvement, favoring other sites such as the lungs. Here we present detailed biological data of an aggressive neuroblastoma subgroup hallmarked by 12q amplification and atypical clinical presentation for which our in vitro studies indicate that CDK4 and/or MDM2 inhibition also could be beneficial.
    Journal
    |
    MDM2 (E3 ubiquitin protein ligase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CDK4 (Cyclin-dependent kinase 4)
    |
    Chr del(11q) • MYCN amplification • CDK4 amplification • MDM2 amplification + CDK4 amplification
    |
    Verzenio (abemaciclib) • Kisqali (ribociclib) • Nutlin-3
    almost2years
    Establishment and characterization of a novel patient-derived cell line of dedifferentiated liposarcoma, NCC-DDLPS6-C1. (PubMed, Hum Cell)
    Anticancer drugs that significantly reduced the proliferation of NCC-DDLPS6-C1 cells were identified by drug library screening. Thus, NCC-DDLPS6-C1 may recapitulate the original genotypes and phenotypes, and we conclude that the NCC-DDLPS6-C1 cell line is a useful resource for the study of DDLPS.
    Preclinical • Journal
    |
    MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
    |
    MDM2 overexpression • MDM2 amplification + CDK4 amplification
    2years
    Primary cardiac undifferentiated pleomorphic sarcoma is associated with TP53 mutation during lack of MDM2 amplification, and targeted sequencing analysis reveals potentially actionable targets. (PubMed, Hum Pathol)
    Several new potentially actionable mutations, including those in RARA, ALK, PTCH1, RET, ROS1, ABL1, and MET, were also found. These findings improve the molecular understanding of this rare malignancy and are expected to provide a basis for developing precision therapeutics for cardiac UPS and intimal sarcomas.
    Journal
    |
    ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • MDM2 (E3 ubiquitin protein ligase) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • PTCH1 (Patched 1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma) • JAK3 (Janus Kinase 3) • GATA1 (GATA Binding Protein 1)
    |
    TP53 mutation • MDM2 amplification • CDKN2A deletion • CDKN2A mutation • CDK4 amplification • PTCH1 mutation • TP53 overexpression • JAK3 mutation • MDM2 overexpression • MDM2 amplification + CDK4 amplification • PDGFRB mutation
    2years
    Establishment and characterization of NCC-DDLPS5-C1: a novel patient-derived cell line of dedifferentiated liposarcoma. (PubMed, Hum Cell)
    Thus, we concluded that the NCC-DDLPS5-C1 cell line could be a useful resource for the study of DDLPS. Considering the diversity of disease in terms of clinical outcomes, continuous efforts are required to develop more patient-derived cancer models with different clinical and pathological backgrounds.
    Preclinical • Journal
    |
    MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
    |
    MDM2 overexpression • MDM2 amplification + CDK4 amplification
    over2years
    Establishment and Characterization of NCC-DDLPS4-C1: A Novel Patient-Derived Cell Line of Dedifferentiated Liposarcoma. (PubMed, J Pers Med)
    Consequently, we identified the histone deacetylase inhibitor romidepsin as a novel candidate drug. In conclusion, the NCC-DDLPS4-C1 cell line is a useful tool for the basic study of DDLPS.
    Preclinical • Journal
    |
    MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
    |
    MDM2 amplification + CDK4 amplification
    |
    Istodax (romidepsin)