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    BIOMARKER:

    miR-138 underexpression + miR-497 overexpression

    i
    Other names: MIR497, MicroRNA 497, Hsa-MiR-497-5p, Hsa-MiR-497-3p, Hsa-Mir-497, MIR497, Hsa-Mir-15-P1c, MIMAT0004768, MIMAT0002820, MI0003138, MIRN497, Mir-497, RF00793
    Entrez ID:
    574456
    5years
    Characterization of genetically defined sporadic and hereditary type 1 papillary renal cell carcinoma cell lines. (PubMed, Genes Chromosomes Cancer)
    All cell lines formed tumor xenografts in athymic nude mice and thus provide in vivo models of type 1 pRCC. These type 1 pRCC cell lines provide a comprehensive representation of the genetic alterations associated with pRCC that will give insight into the biology of this disease and be ideal preclinical models for therapeutic studies.
    Journal
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    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
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    CDKN2A deletion • CDKN2A mutation • miR-138 underexpression + miR-497 overexpression
    5years
    Landscape of Cyclin Pathway Genomic Alterations Across 5,356 Prostate Cancers: Implications for Targeted Therapeutics. (PubMed, Oncologist)
    Alterations in possible resistance genes, RB1 and CCNE1, were detected in 9.7% (up to 54.6% in neuroendocrine) and 1.2% of cases, respectively, whereas AR alterations were seen in 20.9% of tumors (~27.3% in anaplastic). Cyclin sensitizing alterations were also more frequently associated with concomitant AR alterations.
    Journal
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    AR (Androgen receptor) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • CDK6 (Cyclin-dependent kinase 6) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3)
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    CCND1 amplification • CDK4 amplification • miR-138 underexpression + miR-497 overexpression
    5years
    Genomic alterations in thymoma-molecular pathogenesis? (PubMed, J Thorac Dis)
    TCs, however, display a higher mutational burden, with frequent mutations of TP53 and epigenetic regulatory genes and loss of CDKN2A. The knowledge of molecular alterations in TETs fosters the understanding of their pathogenesis and provides guidance for further studies that may lead to the development of targeted therapies.
    Review • Journal • Tumor Mutational Burden
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    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
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    TP53 mutation • TMB-H • TMB-L • miR-138 underexpression + miR-497 overexpression
    5years
    Hhex regulates murine lymphoid progenitor survival independently of Stat5 and Cdkn2a. (PubMed, Eur J Immunol)
    Expression of the anti-apoptotic factor Bcl2, but not activated Stat5, rescued the development of T-, B- and Natural Killer cell lineages in the absence of Hhex. These results indicate that Bcl2 expression, but not Stat5b signaling or loss of Cdkn2a, can overcome the lymphoid deficiencies caused by the absence of Hhex, suggesting that the primary role of this transcription factor is to promote survival of lymphoid progenitors during early lymphoid development.
    Journal
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    BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • STAT5B (Signal Transducer And Activator Of Transcription 5B)
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    BCL2 expression • miR-138 underexpression + miR-497 overexpression
    5years
    [VIRTUAL] Pathogenic Genomic Alterations of CDKN2A Predict Immunotherapy Resistance in NSCLC (IASLC-WCLC 2020)
    ICB included pembrolizumab (n=85, 58%), nivolumab +/- ipilimumab (n=19 monotherapy, n=18 dual blockade, 27%), atezolizumab (n=17, 12%), and durvalumab (n=11, 8%). Conclusion In a large cohort of NSCLC patients treated with ICB, NGS identified CDKN2A mutation/deletion as a predictor of poor clinical outcomes. In the context of recent evidence for sensitivity to CDK4/6 inhibition of CDKN2A-deficient tumors, our findings raise the possibility of utilizing currently available targeted agents in the treatment of CDKN2A-deficient NSCLCs receiving ICB.
    PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
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    TMB-H • CDKN2A deletion • CDKN2A mutation • miR-138 underexpression + miR-497 overexpression
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    Keytruda (pembrolizumab) • Opdivo (nivolumab) • Tecentriq (atezolizumab) • Yervoy (ipilimumab) • Imfinzi (durvalumab)
    5years
    Variable expression of CXCR4 in molecular subtypes of infiltrating gliomas. (PubMed, Clin Neuropathol)
    CXCR4 is expressed in a subset of DIPGs and GBMs, but it is not expressed in astrocytomas or oligodendrogliomas. CXCR4 expression is variable and it is influenced by tumor genomic alterations. It is important to consider CXCR4 expression in clinical trials that evaluate the efficacy of CXCR4 inhibitors in the treatment of gliomas.
    Journal
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    EGFR (Epidermal growth factor receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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    PIK3CA mutation • IDH2 mutation • EGFR expression • miR-138 underexpression + miR-497 overexpression
    5years
    CDKN2A and MTAP Are Useful Biomarkers Detectable by Droplet Digital PCR in Malignant Pleural Mesothelioma: A Potential Alternative Method in Diagnosis Compared to Fluorescence In Situ Hybridisation. (PubMed, Front Oncol)
    Our in-house designed ddPCR assays for MTAP and CDKN2A are useful in differentiating MPM from RMH, and is highly concordant with FISH that is currently used in diagnosing MPM. ddPCR detection of these genetic losses can potentially be utilized as an alternative method in the diagnosis of MPM and for the future development of a less-invasive MPM-specific detection technique on MPM tumor tissue DNA.
    Journal
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    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)
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    CDKN2A deletion • miR-138 underexpression + miR-497 overexpression
    5years
    [VIRTUAL] In search of novel synthetic lethality anti-cancer drug targets in intrahepatic cholangiocarcinoma: MTAP genomic loss. (ASCO-GI 2021)
    Comprehensive genomic profiling elucidated that MTAP GA are frequent in IC and features relatively high GA/tumor, including 9p21 co-deletion, but relatively low TMB and PD-L1 expression. Isolated MTAP deletion without CDKN2A/B co-deletion was extremely rare. In addition to the potential targeting of PRMT5 in MTAP-IC tumors, co-altered genes known to be targets in IC such as FGFR2, IDH1 and BRAF are still prevalent in MTAP-IC, indicating potential for combining targeted therapies in some MTAP-IC patients.
    Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • MSi-H Biomarker • BRCA Biomarker • IO biomarker
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    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) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • MTAP (Methylthioadenosine Phosphorylase) • BAP1 (BRCA1 Associated Protein 1) • SMAD4 (SMAD family member 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • BRCA (Breast cancer early onset) • PRMT5 (Protein Arginine Methyltransferase 5)
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    PD-L1 expression • TP53 mutation • BRAF V600E • KRAS mutation • MSI-H/dMMR • KRAS G12C • HER-2 amplification • BRAF V600 • MET amplification • PD-L1 underexpression • PD-L1 negative • TMB-L • CDKN2A deletion • MTAP deletion • KRAS G12 • CDKN2B deletion • HER-2 amplification + PD-L1 expression • KRAS deletion • miR-138 underexpression + miR-497 overexpression
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    FoundationOne® CDx • PD-L1 IHC 22C3 pharmDx
    5years
    [VIRTUAL] Mutational Profile May Aid in Diagnosis of Undifferentiated/Dedifferentiated Melanoma (ASDP 2020)
    Undifferentiated/dedifferentiated melanoma is a diagnostic challenge by standard immunohistochemical methods. Identification of mutations that are common in melanoma may be a useful adjunct in the diagnosis of these challenging cases.
    IO biomarker
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    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • TSC1 (TSC complex subunit 1) • CD163 (CD163 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • VIM (Vimentin) • TP63 (Tumor protein 63)
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    BRAF V600E • NRAS mutation • BRAF V600 • NRAS Q61K • NRAS Q61 • CDKN2B deletion • miR-138 underexpression + miR-497 overexpression
    5years
    [VIRTUAL] Metastatic Basaloid Squamous Cell Carcinoma of the Tongue with Ductal Differentiation Masquerading as Cutaneous Porocarcinoma (ASDP 2020)
    Two month interval imaging showed a mild, but widespread decrease in tumor burden. This case of HPV-negative basaloid SCC of the tongue with ductal differentiation metastatic to the skin underscores the importance to clinical decision-making of differentiating porocarcinoma from its mimics.
    PD(L)-1 Biomarker • IO biomarker
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    TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PBRM1 (Polybromo 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CDK6 (Cyclin-dependent kinase 6) • EPHB4 (EPH receptor B4)
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    TP53 mutation • PBRM1 mutation • miR-138 underexpression + miR-497 overexpression
    5years
    Chemotherapy impacts on the cellular response to CDK4/6 inhibition: distinct mechanisms of interaction and efficacy in models of pancreatic cancer. (PubMed, Oncogene)
    Since chemotherapy represents the established backbone of PDAC treatment we evaluated the interaction of CDK4/6 inhibitors with gemcitabine and taxanes that are employed in the treatment of PDAC...In contrast, pharmacological inhibition of CDK4/6 yields a cooperative cytostatic effect in combination with docetaxel and prevents adaptation and cell cycle re-entry, which is a common basis for resistance to such agents. Importantly, using organoid and PDX models we could confirm the cooperative effects between chemotherapy and CDK4/6 inhibition in vivo. These data indicate that the combination of cytotoxic and cytostatic agents could represent an important modality in those tumor types that are relatively resistant to CDK4/6 inhibitors.
    Clinical • Journal
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    KRAS (KRAS proto-oncogene GTPase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
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    KRAS mutation • miR-138 underexpression + miR-497 overexpression
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    gemcitabine • docetaxel
    over5years
    [VIRTUAL] Assessment of NTRK Alterations and TRK Inhibitor Therapy: A Single Center Experience (AMP 2020)
    Our cohort displayed occurrence of NTRK fusions in a spectrum ranging from rare solid tumors (infantile fibrosarcoma >75% incidence) to AML (<5% incidence). Demonstration of the remarkable efficacy of larotrectinib and entrectinib in clinical trials led to their accelerated tissue-agnostic US Food and Drug Administration (FDA) approval for adult and pediatric patients with NTRK gene fusion solid tumors. Thus, it appears beneficial to screen all solid tumors without any known oncogenic driver for NTRK fusions.
    Clinical
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NPM1 (Nucleophosmin 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • ETV6 (ETS Variant Transcription Factor 6) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • TPM3 (Tropomyosin 3) • NTRK (Neurotrophic receptor tyrosine kinase)
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    TP53 mutation • NTRK1 fusion • NTRK3 fusion • NPM1 mutation • KRAS G13D • ETV6-NTRK3 fusion • KRAS G13 • TPM3-NTRK1 fusion • IDH2 R140Q • NPM1 W288 • NTRK positive • PIK3CA Q546R • miR-138 underexpression + miR-497 overexpression • NTRK fusion
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    Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)