^
    2ms
    Next-generation sequencing for pediatric CNS tumors: does it add value in a middle-income country setup? (PubMed, Front Oncol)
    Nine patients received targeted therapy; dabrafenib/trametinib (6), pembrolizumab (2), and entrectinib (1), mostly upon tumor progression (7). Outsourcing of NGS testing was feasible; however, criteria for case selection are needed. In addition, local capacity-building in conducting the test, interpretation of the results, and access to "new drugs" continue to be a challenge in LMICs.
    Journal • PD(L)-1 Biomarker • Next-generation sequencing
    |
    BRAF (B-raf proto-oncogene) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK (Neurotrophic receptor tyrosine kinase) • STAT6 (Signal transducer and activator of transcription 6) • NAB2 (NGFI-A Binding Protein 2)
    |
    BRAF mutation • BRAF K601E • BRAF G469A • BRAF K601
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    TruSight RNA Pan-Cancer Panel
    |
    Keytruda (pembrolizumab) • Mekinist (trametinib) • Tafinlar (dabrafenib) • Rozlytrek (entrectinib)
    2ms
    A Study Comparing the Combination of Dasatinib and Chemotherapy Treatment With or Without Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or Philadelphia Chromosome-Like (Ph-Like) ABL-Class B-Cell Acute Lymphoblastic Leukemia (B-ALL) (clinicaltrials.gov)
    P3; Initiation date: Jan 2024 --> Apr 2024
    Trial initiation date
    |
    ABL1 (ABL proto-oncogene 1) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • CD19 (CD19 Molecule) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CSF1R (Colony stimulating factor 1 receptor)
    |
    CD19 expression
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    TruSight RNA Pan-Cancer Panel
    |
    dasatinib • imatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine • Starasid (cytarabine ocfosfate)
    2ms
    Gene Fusions in Aggressive Testicular Leydig Cell Tumors Likely Represent Events Secondary to Genomic Instability without a Driver Role (USCAP 2024)
    TERT fusions were not identified in this series of LCTs, with 2 aggressive metastasizing LCTs harboring non-recurrent NAV3::ASB8 and RAB3IP::TAFA2. These structural variants have not been reported previously and likely represent events secondary to genomic instability without a clear pathogenic role (PMID: 34103665). Whole transcriptome analysis is under way to elucidate additional genomic alterations present in aggressive LCTs.
    MDM2 (E3 ubiquitin protein ligase) • NAV3 (Neuron Navigator 3 )
    |
    MDM2 amplification
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    TruSight RNA Pan-Cancer Panel
    2ms
    Renal Juxtaglomerular Cell Tumors Are Not Driven by Recurrent Gene Fusions: Molecular Analysis of a Multi-Institutional Series (USCAP 2024)
    The results of the present study suggest that gene fusions likely play a minor role in the oncogenesis of JxGCTs. Whether non-recurrent fusions such as TFG::GPR128 identified herein represent driver events or not remains an open question. In challenging cases, assessment with RNA sequencing panels may be helpful to exclude fusion-driven neoplasms that demonstrate significant morphologic overlap.
    Clinical
    |
    STAT6 (Signal transducer and activator of transcription 6) • ADGRG7 (Adhesion G Protein-Coupled Receptor G7) • NAB2 (NGFI-A Binding Protein 2)
    |
    TruSight RNA Pan-Cancer Panel
    4ms
    Spindle cell rhabdomyosarcomas: With TFCP2 rearrangements, and novel EWSR1::ZBTB41 and PLOD2::RBM6 gene fusions. A study of five cases and review of the literature. (PubMed)
    "EWSR1/FUS::TFCP2-rearranged SS-RMS is a rare rhabdomyosarcoma subtype, affecting predominantly young adults with average age at presentation 34 years (median 29.5 years; age range 7-86 years), with a predilection for craniofacial bones, rapid clinical course with frequent bone and lung metastases, and poor prognosis (3-year overall survival rate 28%)."
    Journal • Review
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    Archer® FusionPlex® Sarcoma kit • TruSight RNA Pan-Cancer Panel
    5ms
    GENE FUSIONS ARE A PUTATIVE MECHANISM THAT DIMINISHES SENSITIVITY TO VENETOCLAX-HYPOMETHYLATING AGENTS COMBINATION IN ACUTE MYELOID LEUKEMIA (SIE 2023)
    Appealing patterns of resistance emerged from genomic analysis: the “activating like� signature may help define a specific target among tyrosine kinase inhibitors, while “self-renewal like� patients may benefit from histone deacetylase inhibitors (as we previously published). HOXA genes overexpression open a novel therapeutic options for selected patients.
    FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR1 (Fibroblast growth factor receptor 1) • JAK2 (Janus kinase 2) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ETV6 (ETS Variant Transcription Factor 6) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • CSF3R (Colony Stimulating Factor 3 Receptor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • MECOM (MDS1 And EVI1 Complex Locus) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • BAX (BCL2-associated X protein) • LTBP1 (Latent-transforming growth factor beta-binding protein 1) • CCND2 (Cyclin D2) • DDX5 (DEAD-Box Helicase 5) • BCL11B (BAF Chromatin Remodeling Complex Subunit BCL11B) • PER1 (Period Circadian Clock 1) • TBL1XR1 (TBL1X Receptor 1)
    |
    NRAS mutation • CBL mutation • MECOM rearrangement • PDGFRB mutation
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    TruSight RNA Pan-Cancer Panel
    |
    Venclexta (venetoclax)
    5ms
    IS FLT3 INHIBITION A THERAPEUTIC OPTION FOR TRIPLE NEGATIVE B-CELL ADULT ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS? (SIE 2023)
    To evaluate the effect of FLT3 inhibitors in ALL, we treated ex vivo primary leukemic cells of 6 adult ALL patients (FLT3 mut n=4; FLT3 wt n=2) with increasing concentrations of Gilteritinib, Midostaurin, Crenolanib, Sorafenib and Quizartibin for 24, 48 and 72h. AIRC IG 2019 (Project Code: 23810). Figure 1.
    Clinical
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    FLT3 (Fms-related tyrosine kinase 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • KMT2D (Lysine Methyltransferase 2D) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CREBBP (CREB binding protein) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CSMD1 (CUB And Sushi Multiple Domains 1)
    |
    FLT3 mutation • FLT3 expression • ATM expression
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    TruSight RNA Pan-Cancer Panel
    |
    sorafenib • Xospata (gilteritinib) • Rydapt (midostaurin) • crenolanib (ARO-002)
    6ms
    Next generation sequencing for CNS tumors in children; does it add value in a Middle-Income Country setup? (SNO 2023)
    Eight patients received targeted therapy; Dabrafenib/Trametinib (5), Pembrolizumab (2), Entrectinib (1), while radio-chemotherapy was used in the others. Sent abroad NGS testing was feasible, however local capacity building is necessary. In this highly selected tumor cohort, high percentage of targetable alterations were identified. NGS was helpful to characterize tumors more and to offer alternative therapies.
    Clinical • PD(L)-1 Biomarker • Next-generation sequencing
    |
    BRAF (B-raf proto-oncogene) • NTRK (Neurotrophic receptor tyrosine kinase) • STAT6 (Signal transducer and activator of transcription 6) • NAB2 (NGFI-A Binding Protein 2)
    |
    BRAF mutation • BRAF K601E • BRAF G469A • BRAF K601
    |
    TruSight RNA Pan-Cancer Panel
    |
    Keytruda (pembrolizumab) • Mekinist (trametinib) • Tafinlar (dabrafenib) • Rozlytrek (entrectinib)
    6ms
    A Study Comparing the Combination of Dasatinib and Chemotherapy Treatment With or Without Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or Philadelphia Chromosome-Like (Ph-Like) ABL-Class B-Cell Acute Lymphoblastic Leukemia (B-ALL) (clinicaltrials.gov)
    P3; N=680; Not yet recruiting; Sponsor:National Cancer Institute (NCI)
    New P3 trial
    |
    ABL1 (ABL proto-oncogene 1) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • CD19 (CD19 Molecule) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CSF1R (Colony stimulating factor 1 receptor)
    |
    CD19 expression
    |
    TruSight RNA Pan-Cancer Panel
    |
    dasatinib • imatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • Blincyto (blinatumomab) • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine • Starasid (cytarabine ocfosfate)
    6ms
    Novel Mechanisms of Venetoclax Resistance in Acute Myeloid Leukemia Based on Genomic Rearrangements (ASH 2023)
    Through deep transcriptomic characterization combined with conventional diagnostics, this analysis uncovered novel mechanisms of VEN resistance while confirming established ones. The distinct gene expression patterns may help tailor targeted therapies, with patients showing the "activating-like" signature potentially benefiting from tyrosine kinase inhibitors and those with the "self-renewal like" signature possibly responding well to histone deacetylase inhibitors. Furthermore, HOXA gene overexpression presents an exciting therapeutic opportunity for selected patients.
    IO biomarker
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR (Fibroblast Growth Factor Receptor) • JAK2 (Janus kinase 2) • MCL1 (Myeloid cell leukemia 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ETV6 (ETS Variant Transcription Factor 6) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • CSF3R (Colony Stimulating Factor 3 Receptor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • MECOM (MDS1 And EVI1 Complex Locus) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • BAX (BCL2-associated X protein) • LTBP1 (Latent-transforming growth factor beta-binding protein 1) • CCND2 (Cyclin D2) • DDX5 (DEAD-Box Helicase 5) • BCL11B (BAF Chromatin Remodeling Complex Subunit BCL11B) • PER1 (Period Circadian Clock 1) • GSDMC (Gasdermin C) • TBL1XR1 (TBL1X Receptor 1)
    |
    NRAS mutation • CBL mutation • MCL1 expression • NRAS G13 • MECOM rearrangement • PDGFRB mutation
    |
    TruSight RNA Pan-Cancer Panel
    |
    Venclexta (venetoclax)
    8ms
    Clinical and Molecular Features of Pediatric BCP‑ALL With TSLP Receptor (CRLF2) Expression (SOHO 2023)
    In patients with CRLF2 expression, other molecular rearrangements should be searched to determine the proper risk group.
    Clinical
    |
    ABL1 (ABL proto-oncogene 1) • JAK2 (Janus kinase 2) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • NUP214 (Nucleoporin 214) • P2RY8 (P2Y Receptor Family Member 8) • TSLP (Thymic Stromal Lymphopoietin)
    |
    IKZF1 deletion • CRLF2 mutation
    |
    TruSight RNA Pan-Cancer Panel
    |
    Jakafi (ruxolitinib)
    8ms
    Clinico-pathological spectrum of intracranial mesenchymal tumours, FET::CREB fusion-positive - case series (ECP 2023)
    Methylation profiling was inconclusive apart from a histologically typical AFH case with secondary extension into the intracranial space. While most tumours had no recurrence after complete surgical resection, a case with significant residual tumour and instable genome showed cerebrospinal fluid seeding and multiple spinal tumour implants.
    Clinical
    |
    EWSR1 (EWS RNA Binding Protein 1) • ALPP (Alkaline Phosphatase, Placental) • CD68 (CD68 Molecule) • ATF1 (Activating Transcription Factor 1) • CREB1 (CAMP Responsive Element Binding Protein 1)
    |
    ROS1 positive
    |
    TruSight RNA Pan-Cancer Panel
    12ms
    GENOMIC AND TRANSCRIPTOMIC PROFILING REVEALS NOVEL GENE FUSIONS AND MARKERS OF CLINICAL RESPONSE IN PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA (EHA 2023)
    With novel gene fusions and uncovered associations between the dynamics of MRD decline, TP53 and RUNX1 high burden mutations in this real-world cohort, our dataset provides valuable, clinically relevant insights to the genomic and transcriptomic landscape of children diagnosed with ALL. Pediatric, ALL, Prognosis, Mutation analysis
    Clinical
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCR (BCR Activator Of RhoGEF And GTPase) • PTEN (Phosphatase and tensin homolog) • NOTCH1 (Notch 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • WT1 (WT1 Transcription Factor) • NT5C2 (5'-Nucleotidase Cytosolic II) • PAX5 (Paired Box 5) • TCF3 (Transcription Factor 3) • P2RY8 (P2Y Receptor Family Member 8) • PBX1 (PBX Homeobox 1) • CCND3 (Cyclin D3) • PHF6 (PHD Finger Protein 6)
    |
    TP53 mutation • BCR-ABL1 fusion • RUNX1 mutation • IKZF1 deletion • WT1 mutation • NT5C2 mutation • ETV6 mutation • NT5C mutation • PAX5 fusion • ABL1 deletion
    |
    TruSight RNA Pan-Cancer Panel
    12ms
    GENE FUSIONS AND OTHER GENOMIC EVENTS UNDERLIE VENETOCLAX AND HYPOMETHYLATING AGENT RESISTANCE AND PROVIDE NEW TARGETS IN ACUTE MYELOID LEUKEMIA. (EHA 2023)
    By the association of a deep transcriptomic characterization to conventional diagnostics, our analysis suggested novel mechanisms of resistance to VEN based combinations and detected the established ones. RTKs mutations are widespread within resistant patients, suggesting a potential therapy options. However, mutation in thispathway are redundant and not specific, thus hampering the selection of an appropriate target.
    IO biomarker
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR (Fibroblast Growth Factor Receptor) • JAK2 (Janus kinase 2) • MCL1 (Myeloid cell leukemia 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ETV6 (ETS Variant Transcription Factor 6) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • CSF3R (Colony Stimulating Factor 3 Receptor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • MECOM (MDS1 And EVI1 Complex Locus) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • BAX (BCL2-associated X protein) • LTBP1 (Latent-transforming growth factor beta-binding protein 1) • CCND2 (Cyclin D2) • DDX5 (DEAD-Box Helicase 5) • BCL11B (BAF Chromatin Remodeling Complex Subunit BCL11B) • PER1 (Period Circadian Clock 1) • GSDMC (Gasdermin C) • TBL1XR1 (TBL1X Receptor 1)
    |
    TP53 mutation • NRAS mutation • MCL1 overexpression • CBL mutation • BAX expression • PDGFRB mutation
    |
    TruSight RNA Pan-Cancer Panel
    |
    Venclexta (venetoclax)
    1year
    AALL1631: Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P3, N=475, Recruiting, Children's Oncology Group | Trial completion date: Mar 2027 --> Sep 2027 | Trial primary completion date: Mar 2027 --> Sep 2027
    Trial completion date • Trial primary completion date • Combination therapy
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CSF1R (Colony stimulating factor 1 receptor)
    |
    BCR-ABL1 fusion
    |
    TruSight RNA Pan-Cancer Panel
    |
    imatinib • cytarabine • doxorubicin hydrochloride • cyclophosphamide • ifosfamide • etoposide IV • methotrexate • vincristine • daunorubicin • leucovorin calcium • Oncaspar liquid (pegaspargase) • mercaptopurine • Asparlas (calaspargase pegol-mknl) • thioguanine • Hemady (dexamethasone tablets) • Neupogen (filgrastim) • Starasid (cytarabine ocfosfate) • dexrazoxane
    over1year
    CNS tumor with BCOR internal tandem duplication. (PubMed, Childs Nerv Syst)
    Histopathologic examination of the tumor showed a moderately cellular tumor with microcystic formation, myxoid change, and atypical rosettes resembling Homer Wright rosettes. Illumina TruSight RNA Pan-Cancer NGS of the tumor genome revealed BCOR gene exon 15 internal tandem duplications.
    Journal
    |
    BCOR (BCL6 Corepressor)
    |
    TruSight RNA Pan-Cancer Panel
    over1year
    Differential Diagnosis of Rare Thoracic Tumors Characterized by Gene Rearrangement Using RNA Pan-Cancer Panel (IASLC-ACLC 2022)
    The lung is not only the primary organ, but also the most common metastatic site of sarcoma. The RNA Pan-Cancer Panel is expected to be a very effective tool for rapid and accurate differential diagnosis of thoracic tumors caused by gene rearrangement.
    Pan tumor
    |
    TruSight RNA Pan-Cancer Panel
    over1year
    mRNA Capture Sequencing and RT-qPCR for the Detection of Pathognomonic, Novel, and Secondary Fusion Transcripts in FFPE Tissue: A Sarcoma Showcase. (PubMed, Int J Mol Sci)
    Additionally, recurrently detected secondary fusion transcripts in patients diagnosed with EWSR1-NFATC2-positive sarcoma were confirmed (COPS4-TBC1D9, PICALM-SYTL2, SMG6-VPS53, and UBE2F-ALS2). In conclusion, this study shows that mRNA capture sequencing enhances the detection rate of pathognomonic fusions and enables the identification of novel and secondary fusion transcripts in sarcomas.
    Journal
    |
    CHEK2 (Checkpoint kinase 2) • EWSR1 (EWS RNA Binding Protein 1) • FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor) • BRD4 (Bromodomain Containing 4) • PLAA (Phospholipase A2 Activating Protein) • COPS3 (COP9 Signalosome Subunit 3) • PAX3 (Paired Box 3)
    |
    TruSight RNA Pan-Cancer Panel
    over1year
    IMPLEMENTATION OF A ROUTINE DIAGNOSTIC NEXT GENERATION SEQUENCING PANEL OF FUSION-POSITIVE SARCOMAS: A SINGLE CENTER EXPERIENCE (CTOS 2022)
    Our study supports the role of NGS technologies in improving diagnostic accuracy and classification of sarcomas. Few fusions were actionable by drug therapy. As diagnostic RNA-fusion panels become routinely used in sarcoma referral centers, an increasing number of novel fusions are expected to be documented furthermore supporting the critical role of NGS in routine practice.
    Clinical • Next-generation sequencing
    |
    ALK (Anaplastic lymphoma kinase) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    ALK rearrangement
    |
    TruSight RNA Pan-Cancer Panel
    2years
    Genomic and transcriptomic characterization of benign and malignant struma ovarii (AACR 2022)
    In contrast to cancer arising from the thyroid gland, characterized by BRAFV600E as the most common mutation, malignant SO belongs to RAS-like tumors. The downregulation of tumor suppressors and upregulation of DMRT1 might be implicated in the malignant transformation of SO.
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • EP300 (E1A binding protein p300) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • RAC1 (Rac Family Small GTPase 1) • GNAS (GNAS Complex Locus) • TP63 (Tumor protein 63) • DMRT1 (Doublesex And Mab-3 Related Transcription Factor 1)
    |
    TP53 mutation • BRAF V600E • BRAF V600 • KRAS G12V • KRAS G12 • NRAS Q61 • NRAS Q61R • NRAS G12 • NRAS G13 • NRAS Q61L • KRAS Q61L • NRAS G12V
    |
    TruSight RNA Pan-Cancer Panel
    2years
    Qlucore teams with Semmelweis University on pan-cancer classification (Genomeweb)
    "Qlucore said Thursday that it will collaborate with Semmelweis University in Budapest, Hungary, to develop a novel pan-cancer classification model...In developing the model, the partners will use the Illumina TruSight RNA pan-cancer panel as well as Qlucore analytics and visualization technology."
    Licensing / partnership
    |
    TruSight RNA Pan-Cancer Panel