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    BIOMARKER:

    MTAP mutation

    i
    Other names: MTAP, Methylthioadenosine Phosphorylase, S-Methyl-5'-Thioadenosine Phosphorylase, MSAP, 5’-Methylthioadenosine Phosphorylase, MTA Phosphorylase, MTAPase, C86fus, Epididymis Secretory Sperm Binding Protein, Epididymis Luminal Protein 249, MeSAdo Phosphorylase, HEL-249, DMSMFH, DMSFH, LGMBF, BDMF
    Entrez ID:
    4507
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    1m
    A novel machine learning model integrating clinical and molecular data to predict response to second line treatment in recurrent IDHwtglioblastoma (AIOM 2024)
    Background : Nitrosoureas (lomustine/fotemustine) and antiangiogenic drugs (bevacizumab or regorafenib) are second-line treatment options for patients with recurrent IDHwt-glioblastoma (rGBM). The multi-classification ML model developed in this study was able to identify clinical and molecular signatures of recurrent glioblastoma patients responding to specific second-line treatment with bevacizumab or regorafenib or nitrosoureas.
    Clinical • Machine learning
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    TP53 mutation • EGFR mutation • PTEN mutation • IDH wild-type • MTAP mutation
    |
    FoundationOne® CDx
    |
    Avastin (bevacizumab) • Stivarga (regorafenib) • lomustine • Muphoran (fotemustine)
    5ms
    A novel machine learning (ML) model integrating clinical and molecular data to predict response to second-line treatment in recurrent IDHwt-glioblastoma (rGBM) (ESMO 2024)
    Background: Nitrosoureas (lomustine or fotemustine) and antiangiogenic (bevacizumab or regorafenib) are second-line treatment options for patients with rGBM, but to date predictors or efficacy are lacking. The multi-classification ML model developed in this study was able to identify clinical and molecular signatures of rGBM responding to Bevacizumab,Regorafenib or Nitrosuree. This model could be useful to choose the more effective second-line therapy in rGBM.
    Clinical • Machine learning
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    TP53 mutation • EGFR mutation • PTEN mutation • IDH wild-type • MTAP mutation
    |
    FoundationOne® CDx
    |
    Avastin (bevacizumab) • Stivarga (regorafenib) • lomustine • Muphoran (fotemustine)
    over1year
    Genomic landscape of clinically advanced KRAS wild-type pancreatic ductal adenocarcinoma. (PubMed, Front Oncol)
    PD-L1 high expression was similar between the 2 groups (mutated vs wild-type: 5.7% vs 6%,). GA associated with immune checkpoint inhibitors (ICPIs) response including PBRM1 (mutated vs wild-type: 0.7% vs 3.2%, p <0.0001) and MDM2 (mutated vs wild-type: 1.3% vs 4.4%, p <0.0001) were more likely to be seen in KRAS wild-type PDA.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • MTAP (Methylthioadenosine Phosphorylase) • MDM2 (E3 ubiquitin protein ligase) • PBRM1 (Polybromo 1) • SMAD4 (SMAD family member 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • TMB-H • PD-L1 overexpression • BRAF mutation • PIK3CA mutation • HER-2 mutation • ATM mutation • ARID1A mutation • FGFR2 mutation • KRAS wild-type • RAS wild-type • CDKN2A mutation • PBRM1 mutation • RB1 mutation • SMAD4 mutation • CDKN2B mutation • MDM2 mutation • MTAP mutation
    almost2years
    Characterizing the Genomic Landscape of Micropapillary Variant of Urothelial Carcinoma of the Bladder Harboring Activating Extra-Cellular Mutations of the ERBB2 Gene (USCAP 2023)
    Characterizing the genomic landscape of urothelial carcinoma is an important tool to identify possible diagnostic and prognostic biomarkers that drive tumor progression and dictate treatment response. This study identified KMT2D , RB1 and MTAP as potential important genomic driver co-mutations that differ between ERBB2 ECD-mutated MPUC versus non-MPUC tumors.
    Tumor mutational burden
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • RB1 (RB Transcriptional Corepressor 1) • TERT (Telomerase Reverse Transcriptase) • MTAP (Methylthioadenosine Phosphorylase) • KMT2D (Lysine Methyltransferase 2D) • PRMT5 (Protein Arginine Methyltransferase 5) • MTA2 (Metastasis Associated 1 Family Member 2)
    |
    TP53 mutation • HER-2 mutation • KMT2D mutation • RB1 mutation • MTAP mutation
    almost2years
    Characterizing the Genomic Landscape of Micropapillary Variant of Urothelial Carcinoma of the Bladder Harboring Activating Extra-Cellular Mutations of the ERBB2 Gene (USCAP 2023)
    Characterizing the genomic landscape of urothelial carcinoma is an important tool to identify possible diagnostic and prognostic biomarkers that drive tumor progression and dictate treatment response. This study identified KMT2D , RB1 and MTAP as potential important genomic driver co-mutations that differ between ERBB2 ECD-mutated MPUC versus non-MPUC tumors.
    Tumor mutational burden
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • RB1 (RB Transcriptional Corepressor 1) • TERT (Telomerase Reverse Transcriptase) • MTAP (Methylthioadenosine Phosphorylase) • KMT2D (Lysine Methyltransferase 2D) • PRMT5 (Protein Arginine Methyltransferase 5) • MTA2 (Metastasis Associated 1 Family Member 2)
    |
    TP53 mutation • HER-2 mutation • KMT2D mutation • RB1 mutation • MTAP mutation
    2years
    Novel synthetic lethality drug target in urothelial bladder cancer based on MTAP genomic loss. (PubMed, Urol Oncol)
    When compared with MTAP+ UCB, MTAP- UCB differs in genomic signatures including an increase in potentially targetable alterations but a lower frequency of immunotherapy drug biomarkers. Thus, the genomic landscape in MTAP- UCB may play a role in the design of clinical trials incorporating combination treatment strategies when targeting protein arginine methyltransferase 5 in MTAP- tumors.
    Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker • Synthetic lethality
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • PRMT5 (Protein Arginine Methyltransferase 5)
    |
    TMB-H • MTAP mutation
    |
    FoundationOne® CDx
    2years
    Molecular profile and its clinical impact of IDH1 mutated versus IDH1 wild type intrahepatic cholangiocarcinoma. (PubMed, Sci Rep)
    In advanced setting, in the IDH1m group, the presence of KRAS/NRAS and TP53 mutations negatively impact PFS, whereas the presence of TP53 and PIK3CA mutations negatively impact OS; in the IDH1wt group, only the presence of MTAP mutation negatively impact PFS, whereas the presence of TP53 mutation negatively impact OS. We highlighted several molecular differences with distinct prognostic implications between IDH1m and IDH1wt patients.
    Journal • BRCA Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • CCND1 (Cyclin D1) • MTAP (Methylthioadenosine Phosphorylase) • PBRM1 (Polybromo 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NOTCH2 (Notch 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • RAD21 (RAD21 Cohesin Complex Component)
    |
    TP53 mutation • KRAS mutation • NRAS mutation • PIK3CA mutation • IDH1 mutation • ATM mutation • FGFR2 mutation • CDKN2A mutation • PBRM1 mutation • CDKN2B mutation • IDH wild-type • MTAP mutation • NBN mutation
    |
    FoundationOne® CDx
    over2years
    IDH1 IN INTRAHEPATIC CHOLANGIOCARCINOMA: A COMPARATIVE GENOMIC ANALYSIS AND CLINICAL IMPACT (ILCA 2022)
    We highlighted several molecular differences with distinct prognostic implications between IDH1m and IDH1wt patients.
    Clinical • BRCA Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • CCND1 (Cyclin D1) • MTAP (Methylthioadenosine Phosphorylase) • PBRM1 (Polybromo 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NOTCH2 (Notch 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • RAD21 (RAD21 Cohesin Complex Component)
    |
    TP53 mutation • KRAS mutation • NRAS mutation • PIK3CA mutation • IDH1 mutation • ATM mutation • FGFR2 mutation • CDKN2A mutation • PBRM1 mutation • CDKN2B mutation • IDH wild-type • MTAP mutation • NBN mutation
    |
    FoundationOne® CDx
    over2years
    Clinicopathologic assessment of MTAP status in muscle invasive urothelial carcinoma (ECP 2022)
    Loss of MTAP occurs in <30% of primary muscle invasive urothelial carcinomas. It does not associate with stage suggesting loss is acquired early in the disease. There were no statistically significant association with outcome parameters or neoadjuvant chemotherapy status.
    Clinical
    |
    TP53 (Tumor protein P53) • FGFR3 (Fibroblast growth factor receptor 3) • MTAP (Methylthioadenosine Phosphorylase)
    |
    TP53 mutation • FGFR3 mutation • MTAP mutation
    over2years
    Intrahepatic cholangiocarcinoma (iCCA) genomic findings with high versus low tumor mutational burdens (ESMO 2022)
    Finally, TMB-H cases are enriched in multiple independent biomarkers of response to immunotherapy such as MSI, PD-L1, evolving ones such as PBRM1 and STK11 and depleted in resistance biomarkers such as MTAP. These findings support the clinical development of immunotherapy approaches for the treatment of TMB-H iCCA.
    Tumor Mutational Burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • STK11 (Serine/threonine kinase 11) • ARID1A (AT-rich interaction domain 1A) • MTAP (Methylthioadenosine Phosphorylase) • PBRM1 (Polybromo 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    TP53 mutation • TMB-H • HER-2 amplification • HER-2 mutation • IDH1 mutation • IDH2 mutation • ATM mutation • ARID1A mutation • FGFR2 mutation • TMB-L • FGFR2 fusion • PBRM1 mutation • MTAP mutation
    |
    FoundationOne® CDx
    over2years
    Magnetic-Driven Hydrogel Microrobots Selectively Enhance Synthetic Lethality in MTAP-Deleted Osteosarcoma. (PubMed, Front Bioeng Biotechnol)
    In this study, EPZ015666, a PRMT5 inhibitor, was selected as the synthetic lethality drug... Our magnetic-driven drug delivery system could carry synthetic lethality drugs. Meanwhile, the selective inhibition of this system could be easily controlled by programming the strength of the magnetic field.
    Journal • Synthetic lethality
    |
    MTAP (Methylthioadenosine Phosphorylase) • PRMT5 (Protein Arginine Methyltransferase 5)
    |
    MTAP deletion • MTAP mutation
    |
    EPZ015666
    over2years
    Genomic landscape of non-small-cell lung cancer with methylthioadenosine phosphorylase (MTAP) deficiency. (PubMed, Cancer Med)
    "MTAP loss occurs in 13% of NSCLC, supporting the development of targeted therapies to exploit PRMT5 hyper-dependence. MTAP loss is accompanied by small differences in targeted and immunotherapy options which may impact future combination strategies."
    Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • STK11 (Serine/threonine kinase 11) • RB1 (RB Transcriptional Corepressor 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • MTAP (Methylthioadenosine Phosphorylase) • MDM2 (E3 ubiquitin protein ligase) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • PRMT5 (Protein Arginine Methyltransferase 5)
    |
    PD-L1 expression • KRAS mutation • EGFR mutation • KRAS G12C • KRAS G12 • MTAP mutation
    |
    PD-L1 IHC 22C3 pharmDx