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    GENE:

    FGF3 (Fibroblast growth factor 3)

    i
    Other names: FGF3, Fibroblast Growth Factor 3, V-INT2 Murine Mammary Tumor Virus Integration Site Oncogene Homolog, Murine Mammary Tumor Virus Integration Site 2, Heparin-Binding Growth Factor 3, INT-2 Proto-Oncogene Protein, Proto-Oncogene Int-2, Oncogene INT2, HBGF-3, INT2
    2ms
    Gastrointestinal Stromal Tumors (GISTs) in Pediatric Patients: A Case Report and Literature Review. (PubMed, Children (Basel))
    To illustrate these points, we conclude with a case from our clinic involving a 15-year-old female with multiple CD117-positive gastric GISTs and a quadruple-negative wild-type genetic profile who required urgent surgical intervention following a failed tumor embolization. This case underscores the critical need for early diagnosis and individualized therapeutic strategies combining oncologic and surgical care to improve outcomes in pediatric GIST patients.
    Review • Journal • Stroma
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    KIT (KIT proto-oncogene, receptor tyrosine kinase) • FGF3 (Fibroblast growth factor 3)
    3ms
    The Genomic Landscape of Breast Cancer in Young and Older Women. (PubMed, Clin Breast Cancer)
    Our data suggest distinct molecular aberrations exist between YWBC and OWBC. Exploiting these molecular changes could refine our treatment strategies in YWBC and OWBC.
    Journal • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • AR (Androgen receptor) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • FGF3 (Fibroblast growth factor 3) • FGF4 (Fibroblast growth factor 4)
    4ms
    A pan-tumor description of the genomic, transcriptomic, and immunological landscape of sodium-glucose cotransporter-2 (SGLT2) and association with clinical outcomes. (ASCOBT 2024)
    SCL5A2-H across all investigated tumors was associated with increased immune infiltrate and a T cell-inflamed phenotype in addition to improved survival in multiple cancer types. Future research on SGLT2 should delineate its role in cancer formation versus its association as a potential positive prognostic marker.
    Clinical data • Clinical • PD(L)-1 Biomarker • IO biomarker • Pan tumor
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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) • FGF3 (Fibroblast growth factor 3)
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    PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP142) Assay
    7ms
    Bioinformatics Analysis of Hub Genes in Craniofacial Microsomia Combined With Congenital Heart Disease. (PubMed, J Craniofac Surg)
    This study identified some significant hub genes, pathways, and modules of CFM associated with CHD by bioinformatics analyses. Our findings indicate that gene subfamilies fibroblast growth factor 3, GATA binding protein 3, nuclear factor of activated T cells 1, histone cell cycle regulator, EPAS1, mitogen-activated protein kinase 1, and CRK like proto-oncogene, adaptor protein may have had significant involvement in both CFM and CHD.
    Journal
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    FGF3 (Fibroblast growth factor 3) • EPAS1 (Endothelial PAS domain protein 1) • MAPK1 (Mitogen-activated protein kinase 1) • GATA3 (GATA binding protein 3) • NFATC1 (Nuclear Factor Of Activated T Cells 1)
    7ms
    Concordance between tissue (tumor DNA) and liquid (ctDNA) biopsy next-generation sequencing (NGS) data in detection of PIK3CA, AKT1, and PTEN alterations in breast cancer: A retrospective analysis. (ASCO 2024)
    Background: In the Phase 3 CAPItello-291 trial (NCT04305496), the addition of capivasertib (a potent, selective pan-AKT inhibitor) to fulvestrant significantly improved progression-free survival in patients with HR+/HER2− advanced breast cancer, especially in those with PIK3CA/AKT1/PTEN-altered tumors identified using tissue biopsy-based FoundationOneCDx. PPA between liquid and tissue biopsy NGS data for the detection of PIK3CA/AKT1/PTEN short variants was high in cases with ctDNA TF ≥1%. Liquid biopsies offer a minimally invasive approach for the detection of some CAPItello-291 alterations. However, limitations posed by ctDNA TF <1% and sample and variant types should be considered.
    Retrospective data • BRCA Biomarker • Next-generation sequencing • Circulating tumor DNA • Biopsy • Discordant
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PALB2 (Partner and localizer of BRCA2) • FGF19 (Fibroblast growth factor 19) • CDH1 (Cadherin 1) • FGF3 (Fibroblast growth factor 3) • CHEK2 (Checkpoint kinase 2) • FGF4 (Fibroblast growth factor 4)
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    |
    fulvestrant • Truqap (capivasertib)
    7ms
    Genomic Landscape of Circulating Tumor DNA in Patients With Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor-2-Negative Metastatic Breast Cancer Treated With Abemaciclib: Data From the SCRUM-Japan Cancer Genome Screening Project. (PubMed, JCO Precis Oncol)
    We summarized the ctDNA and cancer tissue mutational landscape, including overall neoplastic burden and PIK3CA and ESR1 hotspot mutations in abemaciclib-treated patients with HR+/HER2- MBC. The data provide insights that could help optimize treatment strategies in this population.
    Journal • Circulating tumor DNA • Metastases
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • FGF3 (Fibroblast growth factor 3) • GATA3 (GATA binding protein 3)
    |
    HR positive • HER-2 negative • PIK3CA mutation • ESR1 mutation • EGFR positive
    |
    Verzenio (abemaciclib)
    8ms
    Comparative molecular profiling of pancreatic ductal adenocarcinoma of the head versus body and tail. (PubMed, NPJ Precis Oncol)
    Differences in IO-related gene expression and TIME cell distribution suggest that response to IO therapies may differ in PDAC arising from H vs. B/T. Subtle differences in the genomic profiles of H vs. B/T tumors were observed.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    KRAS (KRAS proto-oncogene GTPase) • PD-1 (Programmed cell death 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • FGF3 (Fibroblast growth factor 3) • PD-L2 (Programmed Cell Death 1 Ligand 2) • FGF4 (Fibroblast growth factor 4) • IDO1 (Indoleamine 2,3-dioxygenase 1) • FLT4 (Fms-related tyrosine kinase 4) • MUTYH (MutY homolog) • ZNF703 (Zinc Finger Protein 703)
    |
    KRAS mutation • IDO1 expression • CTLA4 expression
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    MI Tumor Seek™
    8ms
    "Examining the link between tooth agenesis and papillary thyroid cancer: is there a risk factor?" Observational study. (PubMed, Prog Orthod)
    Our study suggests a possible link between odontogenesis and PTC. The absence of permanent teeth may increase the likelihood of PTC in women. Leveraging the age-7 orthopantomogram to identify women at high risk for PTC within a critical early detection window could significantly improve oral health outcomes and PTC prognosis through proactive interventions.
    Observational data • Journal
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    FGFR2 (Fibroblast growth factor receptor 2) • FGF3 (Fibroblast growth factor 3) • FGF10 (Fibroblast Growth Factor 10)
    8ms
    Prognostic value of KRAS G12V mutation in lung adenocarcinoma stratified by stages and radiological features. (PubMed, J Thorac Cardiovasc Surg)
    KRAS G12V mutation was associated with aggressive clinical-pathological phenotype and early recurrence. To note, this mutation exhibited significantly worse prognosis in part-solid and stage Ⅰ lung adenocarcinoma patients. Meanwhile, the prognostic significance of KRAS G12C and G12V variants were comparable.
    Journal • PD(L)-1 Biomarker
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    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • KDR (Kinase insert domain receptor) • FGF3 (Fibroblast growth factor 3)
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    PD-L1 expression • KRAS mutation • KRAS G12C • KRAS G12V • RET mutation • KRAS G12
    9ms
    Comprehensive genomic profiling to identify actionable alterations for breast cancer brain metastases in the Chinese population. (PubMed, ESMO Open)
    TMB and TILs were relatively low in BCBMs. Comparable consistency in actionable GAs was identified between BCBMs and matched PTs/ECMs. It was, therefore, logical to carry out genomic testing for BCBMs to identify potential new therapeutic targets when BCBM specimens were available, as ∼31% of samples carried additional actionable GAs.
    Journal • Tumor mutational burden • BRCA Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • KMT2D (Lysine Methyltransferase 2D) • FGF3 (Fibroblast growth factor 3) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • RAD21 (RAD21 Cohesin Complex Component)
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    TP53 mutation • TMB-H • PIK3CA mutation • KMT2D mutation
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    FoundationOne® CDx
    9ms
    Dissection of a CTCF topological boundary uncovers principles of enhancer-oncogene regulation. (PubMed, Mol Cell)
    We show that coordinate disruption of four CTCF motifs in the boundary fuses the adjacent TADs, allows the ANO1 enhancer to contact FGF3, and causes its robust induction. High-resolution micro-C maps reveal specific contact between transcription initiation sites in the ANO1 enhancer and FGF3 promoter that quantitatively scales with FGF3 induction such that modest changes in contact frequency result in strong changes in expression, consistent with a causal relationship.
    Journal
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    FGF3 (Fibroblast growth factor 3) • FGF (Fibroblast Growth Factor) • ANO1 (Anoctamin 1)
    9ms
    Feasibility and clinical utility of blood based NGS in head and neck carcinomas : A single center experience from precision medicine program. (AACR 2024)
    This study demonstrates the feasibility of liquid biopsy in HNSCC and rare head and neck tumors, providing valuable therapeutic and prognostic insights. The findings underscore the potential of liquid biopsy as a valuable tool in clinical decision-making for head and neck cancer patients.
    Clinical • Next-generation sequencing
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    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • DNMT3A (DNA methyltransferase 1) • NOTCH1 (Notch 1) • ASXL1 (ASXL Transcriptional Regulator 1) • FGF19 (Fibroblast growth factor 19) • FGF3 (Fibroblast growth factor 3) • CHEK2 (Checkpoint kinase 2) • STING (stimulator of interferon response cGAMP interactor 1)
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    TP53 mutation • PIK3CA mutation • NOTCH1 mutation • FGF3 amplification
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    FoundationOne® Liquid CDx
    9ms
    Genomic Variability Within Intrinsic Subtypes of Advanced Breast Cancer (USCAP 2024)
    There is a great genomic variability in each intrinsic subtype of advanced BC, with apparently no genomic pattern correlating with each phenotype. Although a transcriptomic test (Prosigna) can help in the classification of the tumors, NGS sequencing with an extended panel allows identifying genetic variants that might benefit the patient with a targeted therapy i a significant percentage of cases.
    BRCA Biomarker • Metastases
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • SF3B1 (Splicing Factor 3b Subunit 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • FGF3 (Fibroblast growth factor 3)
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    HER-2 negative • PTEN mutation • MYC amplification • CCND1 amplification • AKT1 mutation • TP53 amplification
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    Prosigna™ Breast Cancer Prognostic Gene Signature Assay
    11ms
    Real-World comprehensive genomic profiling data for diagnostic clarity in pulmonary Large-Cell neuroendocrine carcinoma. (PubMed, Lung Cancer)
    Large-scale CGP can better characterize biologically distinct molecular subtypes in LCNEC. Further studies to define how these molecular subtypes may help inform treatment decisions in this complex and challenging malignancy are warranted.
    Real-world evidence • Journal • Real-world
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • MTAP (Methylthioadenosine Phosphorylase) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FGF3 (Fibroblast growth factor 3) • MEN1 (Menin 1)
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    TP53 mutation
    |
    FoundationOne® CDx
    12ms
    Functional screening of amplification outlier oncogenes in organoid models of early tumorigenesis. (PubMed, Cell Rep)
    Similarly, FGF3, amplified at 11q13 in 41% of esophageal squamous carcinomas, promoted p53 esophageal organoid growth reversible by small molecule and soluble receptor antagonism of FGFRs. Our studies establish organoid-based contextual screening of candidate genomic drivers, enabling functional evaluation during early tumorigenesis.
    Journal
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    FGF3 (Fibroblast growth factor 3)
    1year
    The Molecular, Immunologic, and Clinicodemographic Landscape of MYC-Amplified Advanced Prostate Cancer. (PubMed, Clin Genitourin Cancer)
    MYC defines a biologically distinct subset of PCa patients and is characterized with multiple proxies of advanced disease. These data suggest that MYC may be prognostic; independent cohorts are needed to validate these findings.
    Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
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    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • FGFR1 (Fibroblast growth factor receptor 1) • CCND1 (Cyclin D1) • FGF3 (Fibroblast growth factor 3) • LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase) • RAD21 (RAD21 Cohesin Complex Component) • ZNF703 (Zinc Finger Protein 703)
    |
    PD-L1 expression • MSI-H/dMMR • MYC amplification • CCND1 amplification
    1year
    Comparison of whole exome, whole transcriptome genomic profiling and targeted sequencing with 50-gene panels (SABCS 2023)
    BC patients (pts) with actionable alterations missed by each 50-gene panel. NS = subtype not specified.
    Tumor mutational burden • BRCA Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • CCND1 (Cyclin D1) • FGF3 (Fibroblast growth factor 3) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
    |
    OncoExTra™ test
    1year
    EMSY amplification co-occurs with FGF/FGFR axis amplification in Metastatic Breast Cancer (SABCS 2023)
    Amplification of EMSY has been mostly reported in ovarian (~17%) and sporadic breast cancers (~13%). EMSY has been reported to behave as an oncogene and a transcriptional repressor. It is well known that it can interact with the BRCA2 protein and potentially contributes to the "BRCAness" of tumors harboring its amp.
    BRCA Biomarker • Metastases
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    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • FGF3 (Fibroblast growth factor 3) • FGF4 (Fibroblast growth factor 4) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting) • ZNF703 (Zinc Finger Protein 703)
    |
    TP53 mutation • PIK3CA mutation • EMSY mutation • FGFR amplification
    1year
    Molecular and immunological landscape of sex-based differences in breast cancer: a distinct disease in men. (SABCS 2023)
    These data indicate that MaBC has a differential mutational frequency, copy number alteration, immune gene expression and immune cell infiltration and overall survival compared to their FeBC counterparts. A better understanding of these sex-based differences with additional research may help inform disease outcomes, provide a rationale for tailored therapeutic approaches and design future treatments. Table 1.
    Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • ASXL1 (ASXL Transcriptional Regulator 1) • BCL6 (B-cell CLL/lymphoma 6) • KMT2D (Lysine Methyltransferase 2D) • RARA (Retinoic Acid Receptor Alpha) • WT1 (WT1 Transcription Factor) • FGF3 (Fibroblast growth factor 3) • CHEK2 (Checkpoint kinase 2) • CREBBP (CREB binding protein) • RAD51B (RAD51 Paralog B) • TSC1 (TSC complex subunit 1) • HLA-DQB1 (Major Histocompatibility Complex, Class II, DQ Beta 1) • FOXA1 (Forkhead Box A1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • CHD1 (Chromodomain Helicase DNA Binding Protein 1) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D) • FLCN (Folliculin) • IL1A (Interleukin 1, alpha) • AMER1 (APC Membrane Recruitment Protein 1) • DAXX (Death-domain associated protein) • HLA-DQB2 (Major Histocompatibility Complex, Class II, DQ Beta 2)
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    TP53 mutation • MSI-H/dMMR • HER-2 negative • HER-2 mutation • STK11 mutation • ASXL1 mutation • ESR1 mutation • CREBBP mutation • AKT1 mutation • TSC1 mutation • MHC-II expression • FLCN mutation • RAD51 mutation
    1year
    Circulating tumor DNA mutation landscape in HR+/HER2− patients with mBC treated with cyclin-dependent kinase 4/6 inhibitors in the SCRUM-Japan MONSTAR-SCREEN study (SABCS 2023)
    Fulvestrant with or without gonadotropin-releasing hormone (55%), letrozole (24%), and anastrozole (11%) were the most common concomitant drugs. PIK3CA alterations were the most frequently detected genetic alterations in both pre- and post- abemaciclib Tx patients with HR+/HER2− mBC. Patients with prior ET had more frequent ESR1 alterations and higher neoplastic burden. Evidence from this study provides insight into the ctDNA dynamics and potential resistance mechanisms in patients with HR+/HER2− mBC.
    Clinical • Circulating tumor DNA
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RB1 (RB Transcriptional Corepressor 1) • CDK4 (Cyclin-dependent kinase 4) • FGF3 (Fibroblast growth factor 3) • GATA3 (GATA binding protein 3)
    |
    HR positive • HER-2 negative • HER-2 mutation • EGFR positive
    |
    FoundationOne® Liquid CDx
    |
    Verzenio (abemaciclib) • fulvestrant • letrozole • anastrozole
    1year
    Cell Cycle Regulators Across Solid Tumors (AMP 2023)
    Across solid tumors, alterations associated with sensitivity to CDK4/6 inhibitors varied widely in frequency. Though the frequency of alterations in CDK4/6 inhibitor resistance genes was generally low, identifying such patients may be critical for decisions regarding the use of CDK4/6 inhibitors.
    Tumor mutational burden
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FGF3 (Fibroblast growth factor 3)
    |
    TMB-H • HER-2 negative • CCNE1 mutation
    |
    OncoExTra™ test
    1year
    Genomic Variations in Esophageal Squamous Cell Carcinoma and Esophageal Adenocarcinoma. (PubMed, Cureus)
    Conclusions Notably, this study showed distinct differences in gene alterations between ESCC and EAC, thereby enhancing our understanding of the genetic landscape of these tumors. Further research is required to elucidate the functional implications of these genetic variations to develop targeted therapies that can improve the prognosis of patients with esophageal cancer.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • NOTCH1 (Notch 1) • TACC3 (Transforming acidic coiled-coil containing protein 3) • FGF19 (Fibroblast growth factor 19) • SMAD4 (SMAD family member 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FGF3 (Fibroblast growth factor 3) • FGF4 (Fibroblast growth factor 4)
    1year
    Primer on FGF3. (PubMed, Differentiation)
    While recent studies indicate of some FGF3 presence in post-natal stages, emerging evidences of its upregulation in various human tumors and cariogenic processes in mouse models, highlights the importance of its close regulation in adult tissues. Altogether, the broad and dynamic expression pattern and regulation of FGF3 in embryonic and adult tissues together with its link to congenital malformations and cancer, calls for further discoveries of its diverse roles in health and disease.
    Journal
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    FGF3 (Fibroblast growth factor 3)
    1year
    Elucidating Fibroblast Growth Factor-induced kinome dynamics using targeted mass spectrometry and dynamic modeling. (PubMed, Mol Cell Proteomics)
    Our system-wide kinase activity data, supplemented with (phospho)proteomics data, reveal ligand-dependent distinct pathway dynamics, elucidate the involvement of not earlier reported kinases such as MARK, and revise some of the pathway effects on biological outcomes. In addition, logic-based dynamic modeling of the kinome dynamics further verifies the biological goodness-of-fit of the predicted models and reveals BRAF-driven activation upon FGF2 treatment, and ARAF-driven activation upon FGF4 treatment.
    Journal
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    BRAF (B-raf proto-oncogene) • FGF19 (Fibroblast growth factor 19) • FGF3 (Fibroblast growth factor 3) • FGF4 (Fibroblast growth factor 4) • FGF2 (Fibroblast Growth Factor 2) • ARAF (A-Raf Proto-Oncogene) • FGF (Fibroblast Growth Factor) • FGF10 (Fibroblast Growth Factor 10)
    over1year
    Comprehensive genomic profiling of penile squamous cell carcinoma and the impact of human papillomavirus status on immune-checkpoint inhibitor-related biomarkers. (PubMed, Cancer)
    Penile squamous cell carcinoma (pSCC) is a rare and aggressive malignancy in the advanced setting, with poor prognosis and little success with immune-checkpoint inhibitors (ICIs) in an unselected patient approach. Human papillomavirus (HPV) infection is a known risk factor for pSCC; its impact on genomic tumor profiling is less defined. Using next-generation sequencing, we explored the genetic landscape and ICI-related biomarkers of pSCC and HPV-driven oncogenic molecular signatures. Our results indicate that HPV-positive and HPV-negative pSCCs are molecularly distinct tumors. Increased tumor mutational burden is associated with HPV-positive tumors, and could serve as a biomarker for predicting therapeutic response to ICI-based therapies. Our results support the growing literature indicating that HPV status in pSCC can be used to guide patient stratification in ICI-based clinical trials.
    Checkpoint inhibition • Journal • Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • KMT2C (Lysine Methyltransferase 2C) • FGF3 (Fibroblast growth factor 3)
    |
    PD-L1 expression • TMB-H • MSI-H/dMMR • PIK3CA mutation • CDKN2A mutation • KMT2C mutation • FGF3 amplification • MLL3 mutation
    |
    VENTANA PD-L1 (SP142) Assay
    over1year
    A cuproptosis-related lncRNA signature predicts the prognosis and immune cell status in head and neck squamous cell carcinoma. (PubMed, Front Oncol)
    A novel CRL-related signature has the potential of prognosis prediction in HNSCC. Targeting CRLs may be a promising therapeutic strategy for HNSCC.
    Journal • Immune cell
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    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • FGF3 (Fibroblast growth factor 3) • TIAM1 (TIAM Rac1 Associated GEF 1) • CDKN2A-DT (CDKN2A Divergent Transcript) • MIR9-3 (MicroRNA 9-3) • TCEA3 (Transcription Elongation Factor A3)
    over1year
    Fibroblast growth factor 3 promotes spontaneous mammary tumorigenesis in Tientsin albino 2 mice via the FGF3/FGFR1/STAT3 pathway. (PubMed, Front Oncol)
    Inhibition of STAT3 or Akt phosphorylation promoted the expression of FGFR1. Validating the conclusions obtained in this study in human breast cancer (HBC) may contribute to targeted therapy and it is worth exploring whether the homologous sequences of MMTV in HBC have a similar oncogenic effect.
    Preclinical • Journal
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    FGFR1 (Fibroblast growth factor receptor 1) • FGF3 (Fibroblast growth factor 3)
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    FGFR1 expression
    over1year
    Sex-based differences in genomic alterations and biomarkers in anal squamous cell carcinoma (ASCC) (ESMO 2023)
    Conclusions The higher incidence of HPV positivity in F compared to M remains the main hypothesis to justify the better prognosis of ASCC in women. A large proportion of PD-L1+ and TMB-High (∼70%), PIK3CA alterations (∼30%) and BRCA1/2 gene alteration (5%) may predict response to possible new therapeutic approaches for pts with ASCC like immunotherapy, targeted tyrosine kinase inhibitors, platinum chemotherapy and PARP inhibitors.
    Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • BRCA Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • KMT2D (Lysine Methyltransferase 2D) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FGF3 (Fibroblast growth factor 3) • CREBBP (CREB binding protein) • FGF4 (Fibroblast growth factor 4)
    |
    PD-L1 expression • BRCA2 mutation • BRCA1 mutation • TMB-H • CCND1 amplification • BRCA1 mutation + BRCA2 mutation
    |
    FoundationOne® CDx
    over1year
    Multiple Alterations of TP53 Predict Worse Clinical Outcome for Oral Cavity Squamous Cell Carcinoma (AMP Europe 2023)
    Other than TP53 double or triple mutations, other gene alterations did not show any clinically significant ACMR or DFS including TERT PM. Limitations of this study include small size of the cohort and relatively short duration of follow- up. The predictive roles of more than 1 TP53 are under further investigation for a larger cohort with multivariant analysis and functional studies.
    Clinical • Clinical data • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • TERT (Telomerase Reverse Transcriptase) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • FGF3 (Fibroblast growth factor 3) • CASP8 (Caspase 8)
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    PD-L1 expression • TP53 mutation • PIK3CA mutation • TERT mutation • TERT promoter mutation
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    PD-L1 IHC 22C3 pharmDx • TruSight Oncology 500 Assay
    over1year
    Clinical Application of Liquid Biopsy across Pan- Cancer: 4baseCare's Experience Using TarGT Indiegene- Liquid Biopsy NGS Panel (AMP Europe 2023)
    The MRD estimation was evident in a breast cancer patient with ERBB2 amplification detected while the patient was on maintenance trastuzumab... This pan- cancer pilot study using the TarGT Indiegene Liquid Biopsy Panel supports the hypothesis that molecular information obtained from liquid biopsy can play a significant role in clinical decision-making, in addition to tissue mutation profiling. The results of this study demonstrate the potential clinical utility of this liquid biopsy panel in identifying actionable genomic alterations in patients with advanced stage cancer. These findings suggest that liquid biopsy has the potential to complement tissue biopsy and provide important molecular information to inform personalized treatment decisions for patients with cancer.
    Clinical • Liquid biopsy • Next-generation sequencing • Biopsy
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    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CCND1 (Cyclin D1) • FGF3 (Fibroblast growth factor 3) • BICC1 (BicC Family RNA Binding Protein 1)
    |
    HER-2 amplification • PIK3CA mutation • FGFR2 fusion • CCND1 amplification • FGF3 amplification
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    Herceptin (trastuzumab)
    over1year
    PD-L1 expression in patients with multiple tumors and their correlation with genomic mutations. (ASCO 2023)
    For patients with multiple tumors, inter-tumoral heterogeneity of PD-L1 expression is common. Several actionable gene mutations were found to be more commonly occurred in PD-L1-heterogenous tumors. Physicians should carefully consider PD-L1 and genomic assessments by case in order to select appropriate patients for ICI treatments.
    Clinical • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • FGF3 (Fibroblast growth factor 3)
    |
    PD-L1 expression • EGFR mutation • EGFR exon 19 deletion • EGFR expression • EGFR wild-type • PD-L1 negative • ALK mutation • PD-L1 mutation
    |
    PD-L1 IHC 22C3 pharmDx • PD-L1 IHC 28-8 pharmDx
    over1year
    Comprehensive profiling of clock genes expression in hepatocellular carcinoma (HCC). (ASCO 2023)
    This is the most extensive profiling study to investigate the expression of clock genes in HCC. Our data show that clock genes expression impacts patient survival and is associated with alterations in immune-related gene expression and TIS score which suggest a role in the modulation of anti-tumor immunity. These results support the clock pathway role as a oncogenic driver and its potential as a therapeutic target in HCC.
    Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • TERT (Telomerase Reverse Transcriptase) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • FGF3 (Fibroblast growth factor 3) • PD-L2 (Programmed Cell Death 1 Ligand 2) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CRY1, Cryptochrome Circadian Regulator 1, • WEE1 (WEE1 G2 Checkpoint Kinase) • ARNTL (Aryl Hydrocarbon Receptor Nuclear Translocator Like) • CLOCK (Clock Circadian Regulator) • PER1 (Period Circadian Clock 1) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule) • NR1D1 (Nuclear Receptor Subfamily 1 Group D Member 1)
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    PD-L1 expression • MSI-H/dMMR • TERT mutation • CRY1 mutation
    over1year
    Racial Disparities in Pathological Complete Response Among Patients Receiving Neoadjuvant Chemotherapy for Early-Stage Breast Cancer. (PubMed, JAMA Netw Open)
    In this cohort study of patients with breast cancer, racial disparities in response to NACT were associated with disparities in survival and varied across different breast cancer subtypes. This study highlights the potential benefits of better understanding the biology of primary and residual tumors.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • CCND1 (Cyclin D1) • MCL1 (Myeloid cell leukemia 1) • FGF3 (Fibroblast growth factor 3) • FAT1 (FAT atypical cadherin 1) • FGF4 (Fibroblast growth factor 4) • ERCC3 (ERCC Excision Repair 3, TFIIH Core Complex Helicase Subunit)
    |
    HER-2 mutation • PTEN mutation • HR negative
    over1year
    M1 macrophage predicted efficacy of neoadjuvant camrelizumab combined with chemotherapy vs chemotherapy alone for locally advanced ESCC: A pilot study. (PubMed, Front Oncol)
    This study compared the efficacy of camrelizumab in combination with neoadjuvant DCF (docetaxel, cisplatin and fluorouracil), with DCF alone for ESCC, and exploring biomarkers related to immune infiltration of the ESCC immunotherapy response. Neoadjuvant camrelizumab combined with chemotherapy improved ORR in locally advanced ESCC. M1-type tumor-associated macrophages and CD56dim NK cells might be utilized to predict camrelizumab efficacy.
    Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • FGF3 (Fibroblast growth factor 3) • FGF4 (Fibroblast growth factor 4)
    |
    cisplatin • docetaxel • 5-fluorouracil • AiRuiKa (camrelizumab)
    over1year
    Clinical management of molecular alterations identified by high throughput sequencing in patients with advanced solid tumors in treatment failure: Real-world data from a French hospital. (PubMed, Front Oncol)
    Treatment with genotype-directed therapy had no impact on overall survival (13 months vs. 14 months; p = 0.95; hazard ratio = 1.04 (95% confidence interval, 0.48-2.26)]. This study highlights that an organized center with a Multidisciplinary Molecular Tumor Board and an NGS screening system can obtain satisfactory results comparable with those of large centers for including patients in clinical trials.
    Real-world evidence • Journal • Tumor mutational burden • Real-world • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • FGF19 (Fibroblast growth factor 19) • SMAD4 (SMAD family member 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FGF3 (Fibroblast growth factor 3)
    |
    FoundationOne® CDx
    over1year
    Cancer associated fibroblast crosstalk through VEGF increases tumor cell proliferation in human pancreatic ductal adenocarcinoma (AACR 2023)
    Interactions between cancer cells and CAFs compound the complexity of the biology of the TME and contribute to poor patient outcomes; therefore, we have put forth a model that better represents these interactions through patient matched PDO - CAF cocultures. Using this model, we demonstrate a novel interaction through VEGF that enhances tumor cell proliferation. We introduce a targeted approach to investigating the complex biology of the TME to inform the mechanisms driving cancer biology in individual patients that can also be used to develop novel therapeutic targets.
    Tumor cell
    |
    KDR (Kinase insert domain receptor) • VEGFA (Vascular endothelial growth factor A) • FGF3 (Fibroblast growth factor 3) • CD79A (CD79a Molecule) • IL6R (Interleukin 6 receptor) • RSPO1 (R-Spondin 1)
    over1year
    The heterogeneous immune and molecular landscape of endometrial cancer metastases (AACR 2023)
    ECM to GU (n=29, HR: 1.59, 570 days, p=0.04) had worse post-Carboplatin survival than ECP (n=3023, 1096 days) while ECM to Lung had better (n=279, HR: 0.73, 1602 days, p=<0.01). ECM to Liver (PD-1/PD-L1i: n=27, HR: 2.4, 165 days, p=<0.01; Bevacizumab: n=44, HR: 1.5, 286 days, p=0.03) had worse post-tx survival compared to ECP (PD-1/PD-L1i: n=607, 760 days; Bevacizumab: n=693, 463 days). ECM to Bone and GU organs have unique molecular alterations when compared to ECP of the uterus and have lower infiltration of immune cells. We also highlight differences in OS when comparing different ECM.
    Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PGR (Progesterone receptor) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ARID1A (AT-rich interaction domain 1A) • PD-1 (Programmed cell death 1) • ASXL1 (ASXL Transcriptional Regulator 1) • FGF19 (Fibroblast growth factor 19) • KMT2D (Lysine Methyltransferase 2D) • RNF43 (Ring Finger Protein 43) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • FGF3 (Fibroblast growth factor 3)
    |
    PD-L1 expression • TMB-H • MSI-H/dMMR • HER-2 amplification • HER-2 amplification + PD-L1 expression
    |
    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
    |
    Avastin (bevacizumab) • carboplatin • gemcitabine
    over1year
    Genetic Characteristics of Primary Cutaneous Malignant Melanoma in Koreans Compared With Western Populations. (PubMed, In Vivo)
    These results clearly demonstrated differences in genetic alterations between melanomas in Asian and Western populations. Therefore, BRAF V600 mutation should be considered a significant signaling pathway explaining melanoma pathogenesis occurrence in both Asian and Western populations, whereas loss of chromosome 9p21.3 is unique to melanomas in Western populations.
    Retrospective data • Journal
    |
    BRAF (B-raf proto-oncogene) • FGF19 (Fibroblast growth factor 19) • CDK4 (Cyclin-dependent kinase 4) • FGF3 (Fibroblast growth factor 3) • FGF4 (Fibroblast growth factor 4)
    |
    BRAF mutation • BRAF V600
    over1year
    Molecular Signature of Biological Aggressiveness in Clear Cell Sarcoma of the Kidney (CCSK). (PubMed, Int J Mol Sci)
    Treatment with FGF3 of BCOR-ITD HEK-293 cell line induced a significant increase in cell migration versus both untreated and scramble cell clone. The identification of over-expressed genes in metastatic CCSKs, with a particular focus on FGF3, could offer new prognostic and therapeutic targets in more aggressive cases.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • FGF3 (Fibroblast growth factor 3) • BCOR (BCL6 Corepressor) • SPP1 (Secreted Phosphoprotein 1)
    |
    TMB-L • VEGFA overexpression • FGF3 overexpression