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    GENE:

    TMB (Tumor Mutational Burden)

    i
    Other names: TMB | Tumor Mutational Burden
    24h
    Longitudinal ultra-sensitive mutation burden sequencing for precise minimal residual disease assessment in AML. (PubMed, Nat Commun)
    The ROC area under curve (AUC) is 0.98 when predicting relapse within 30 weeks of CR timepoint 2 (N = 20). Furthermore, we demonstrate quantitating VAF below 0.01% is essential for accurate relapse prediction.
    Journal • Tumor mutational burden • Minimal residual disease
    |
    TMB (Tumor Mutational Burden) • NPM1 (Nucleophosmin 1)
    |
    NPM1 mutation
    24h
    Base-excision repair pathway shapes 5-methylcytosine deamination signatures in pan-cancer genomes. (PubMed, Nat Commun)
    We validate our findings by modeling BER deficiencies in isogenic cell models. Here, we establish MBD4 as the main actor responsible for 5mC deamination repair in humans.
    Journal • Tumor mutational burden • Pan tumor
    |
    TMB (Tumor Mutational Burden) • MBD4 (Methyl-CpG Binding Domain 4, DNA Glycosylase)
    |
    TMB-L
    1d
    Tissue-based Next Generation Sequencing (NGS) for Patients with Advanced Solid Tumors: the experience of Verona University Hospital (AIOM 2024)
    Our study provides an example of implementation of molecular profiling in an academic pre-screening program. Further analysis will investigate treatment matching rates, drug access schemes, and their impact on treatment efficacy and survival.
    Clinical • Next-generation sequencing • BRCA Biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
    |
    BRAF V600E • KRAS mutation • BRCA2 mutation • BRCA1 mutation • EGFR mutation • KRAS G12C • HER-2 amplification • PIK3CA mutation • BRAF V600 • NTRK1 fusion • PTEN mutation • KIT mutation • FGFR2 mutation • RET mutation • MET mutation • KRAS G12 • ESR1 mutation • NTRK1 mutation • BRAF amplification
    |
    FoundationOne® CDx • TruSight Oncology 500 Assay
    1d
    Durvalumab plus cisplatin and gemcitabine as first line therapy for advanced biliary tract carcinoma (aBTC): a monocentric retrospective experience (AIOM 2024)
    The data presented in this study are consistent with the results of TOPAZ1 trial. However about a third of patients do not respond to CHT or have a short response duration. In our experience both NLR and basal elevated AST/ALT seem to be associated with an improved mPFS and a better outcome but further studies are needed.
    Retrospective data • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden)
    |
    TP53 mutation • KRAS mutation • TMB-H • TMB-L
    |
    TruSight Oncology 500 Assay
    |
    cisplatin • Imfinzi (durvalumab) • gemcitabine
    1d
    Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (AIOM 2024)
    4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.
    Clinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)
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    BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • PIK3CA mutation • MET amplification • ALK rearrangement • FGFR1 amplification • POLE mutation • NF1 mutation • MDM2 amplification • RET mutation • PTCH1 mutation • NF2 mutation • ROS1 mutation • BRCA mutation • ALK rearrangement + PIK3CA mutation • PTCH1 rearrangement • NTRK fusion
    |
    FoundationOne® CDx
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)
    1d
    Genomic alterations in circulating tumor DNA (ctDNA) and response to ABBV-400 treatment in patients with advanced solid tumors (AIOM 2024)
    The ADC ABBV-400 comprises the c-Met–targeting antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor payload. ABBV-400 showed promising preliminary efficacy, with molecular and radiographic responses in pts with advanced solid tumors with heterogeneous genomic profiles, including pts with high TMB and KRAS mutations.
    Clinical • Tumor mutational burden • Circulating tumor DNA • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • MSI (Microsatellite instability) • LRP1B (LDL Receptor Related Protein 1B) • PTPRT (Protein tyrosine phosphatase receptor type T)
    |
    KRAS mutation • TMB-H • MET overexpression • PTPRT mutation
    |
    GuardantINFINITY™
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    telisotuzumab adizutecan (ABBV-400) • telisotuzumab (h224G11)
    1d
    Homologous recombination (HR) and DNA damage repair (DDR) somatic alterations in metastatic colorectal cancer (mCRC): results from the comprehensive genomic profiling (CGP) trial FPG500 (AIOM 2024)
    Background : Treatment (tx) of MSS/MMRp mCRC relies mainly on oxaliplatin (oxa)- or irinotecan-based doublet chemotherapy regimens, with no biomarker reported so far, allowing the selection of one tx over the other. HR-DDRa is associated with MSI-H or TMB-H. Pts with MSS HR-DDRa tumors benefit from oxa-based first line treatment. Longer FU, allowing mature OS data, and wider cohorts are warranted.
    Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • Metastases
    |
    TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCL (FA Complementation Group L) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    TMB-H • MSI-H/dMMR
    |
    TruSight Oncology 500 Assay
    |
    oxaliplatin • irinotecan
    1d
    A novel mouse model recapitulating the MMR-defective SCLC subtype uncovers an actionable sensitivity to immune checkpoint blockade. (PubMed, J Cancer Res Clin Oncol)
    We propose a novel RPM mouse model as a suitable system to mimic MMR-defective SCLC and tumors with high TMB. We provide in vivo evidence that Msh2 deficiency enhances ICI sensitivity. These findings could contribute to stratifying SCLC patients to immunotherapy, thereby improving treatment outcomes.
    Preclinical • Journal • Checkpoint inhibition • Tumor mutational burden • IO biomarker • Checkpoint block
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • RB1 (RB Transcriptional Corepressor 1) • MSH2 (MutS Homolog 2)
    |
    TMB-H
    1d
    Effective treatment strategies and key factors influencing therapeutic efficacy in advanced SMARCA4-deficient non-small cell lung cancer. (PubMed, Lung Cancer)
    The addition of ICIs to local treatment shows promising results for locally advanced patients with SD-NSCLC, and first-line ICIs are associated with improved survival in metastatic SD-NSCLC. STK11/KEAP1 mutations may be linked to reduced efficacy of immunotherapy.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    PD-L1 expression • STK11 mutation • KEAP1 mutation
    1d
    Natural killer cell biology and therapy in multiple myeloma: challenges and opportunities. (PubMed, Exp Hematol Oncol)
    Thus, NK cells can naturally work in tandem with anti-MM therapies and be strategically modulated for improved anti-MM effect. This review article describes immunotypic and phenotypic differences in NK cells along with the functional changes in homeostatic and malignant states and provides expert insights on strategies to harness the potential of NK cells for improving outcomes in MM.
    Review • Journal • Tumor mutational burden
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    TMB (Tumor Mutational Burden) • NCAM1 (Neural cell adhesion molecule 1) • FCGR3A (Fc Fragment Of IgG Receptor IIIa)
    |
    TMB-L
    2d
    Developing hypoxia and lactate metabolism-related molecular subtypes and prognostic signature for clear cell renal cell carcinoma through integrating machine learning. (PubMed, Discov Oncol)
    We have developed a novel prognostic signature that integrates hypoxia and lactate metabolism. It is expected to become an effective tool for prognosis prediction, immunotherapy and personalized medicine of ccRCC.
    Journal • Tumor mutational burden • IO biomarker • Machine learning
    |
    TMB (Tumor Mutational Burden)
    2d
    Integrated profile of tumor stage and mutational burden predicts disparate clinical responses to immune checkpoint inhibitors: A risk-benefit study. (PubMed, Semin Oncol)
    This may require enrolling patients with less-severe or early-stage disease to enable long-term follow-up with effective clinical surveillance. By comprehensively evaluating the added benefit of improved treatment efficacy and the potential risk of adverse treatment outcome, a risk-benefit profile can optimize immunotherapy regimens, with profound implications for clinical decision-making and regulatory approvals of ICI.
    Journal • Checkpoint inhibition • Benefit-risk assessment • Tumor mutational burden • IO biomarker
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    TMB (Tumor Mutational Burden)
    |
    TMB-H • TMB-L
    2d
    Machine learning-derived natural killer cell signature predicts prognosis and therapeutic response in clear cell renal cell carcinoma. (PubMed, Transl Oncol)
    Intricate signaling interactions between NK cells and various cellular subgroups were depicted and the developmental trajectory of NK cells was elucidated. A NK cells-related risk model was established, which can provide reliable prognostic information and identified patients with more probability of benefiting from therapy.
    Journal • Tumor mutational burden • IO biomarker • Machine learning
    |
    TMB (Tumor Mutational Burden)
    2d
    Genetic Alterations in Chromatin Regulatory Genes in Upper Tract Urothelial Carcinoma and Urothelial Bladder Cancer. (PubMed, Cancer Med)
    Since genetic alterations of the chromatin pathway genes are important in both UTUC and UCB, they could serve as potential biomarkers for predicting disease progression and therapeutic targets. Differences in mutation frequencies of DDR pathway, TMB, CNV, and TCR might be the contributing factors for the distinct responses to immune checkpoint inhibitor (ICI) between UTUC and UCB.
    Journal • Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden) • ARID1A (AT-rich interaction domain 1A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • KMT2C (Lysine Methyltransferase 2C) • EP300 (E1A binding protein p300) • GATA3 (GATA binding protein 3)
    |
    ARID1A mutation • EP300 mutation
    2d
    Analysis of the treatment efficacy and prognostic factors of PD-1/PD-L1 inhibitors for advanced gastric or gastroesophageal junction cancer: a multicenter, retrospective clinical study. (PubMed, Front Immunol)
    Factors for improved PFS include early treatment, lower T stage, fewer metastatic sites, and lower pre-IBIL, post-GLOB, and post-CA125 levels. Nomogram models can help identify patients who may benefit from immunotherapy, providing valuable clinical guidance.
    Retrospective data • Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MUC16 (Mucin 16, Cell Surface Associated) • CA 19-9 (Cancer antigen 19-9)
    2d
    Tumor-related IGF2BP1-derived molecular subtypes to predict prognosis and immune microenvironment in head and neck squamous cell carcinoma. (PubMed, Front Immunol)
    This study highlights the crucial link between RNA modification and TME diversity. Evaluating RNA modification in tumors improves our understanding of TME features and supports the development of effective immunotherapy strategies.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • IGF2BP1 (Insulin Like Growth Factor 2 MRNA Binding Protein 1)
    |
    PD-L1 expression • PD-L1-L
    2d
    Exploring the role of mitophagy-related genes in breast cancer: subtype classification and prognosis prediction. (PubMed, Int J Med Sci)
    This nomogram was validated and showed good predictive performance, with area under the curve (AUC) values for 1-year, 3-year, and 5-year OS of 0.895, 0.765, and 0.728, respectively. Our findings underscore the profound impact of prognostic genes on the immune response and prognostic outcomes in BC, indicating that they can provide new avenues for personalized BC treatment and potentially improve clinical outcomes.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • CHI3L1 (Chitinase 3-like 1) • CLIC6 (Chloride Intracellular Channel 6) • PRKAA2 (Protein Kinase AMP-Activated Catalytic Subunit Alpha 2)
    |
    TMB-L
    3d
    The Prognostic Value and Immunotherapeutic Characteristics of GFPT2 in Pan-cancer. (PubMed, Comb Chem High Throughput Screen)
    Collectively, GFPT2 is potentially useful as a biomarker for prognostic prediction and immune infiltration in a variety of malignancies ,and could lead to exciting new approaches to personalized oncotherapy.
    Journal • Tumor mutational burden • PARP Biomarker • IO biomarker • Pan tumor
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • GFPT2 (Glutamine-Fructose-6-Phosphate Transaminase 2)
    |
    Lynparza (olaparib) • Lenvima (lenvatinib) • Tasigna (nilotinib)
    3d
    Randomized Phase II Study of Durvalumab with or without Tremelimumab in Patients with Metastatic Castration Resistant Prostate Cancer. (PubMed, Clin Cancer Res)
    D+T is active in mCRPC but patient selection remains a challenge. Further studies to develop predictive biomarkers are warranted.
    P2 data • Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8)
    |
    TMB-H • PD-L1 overexpression
    |
    Imfinzi (durvalumab) • Xtandi (enzalutamide capsule) • Imjudo (tremelimumab) • abiraterone acetate
    3d
    Genomic profiling and clinical utility of circulating tumor DNA in metastatic prostate cancer: SCRUM-Japan MONSTAR SCREEN project. (PubMed, BJC Rep)
    This study revealed valuable findings for the clinical care of metastatic prostate cancer. Especially, predictive factors such as HRR defect in mCSPC should be validated in the future.
    Journal • Tumor mutational burden • Circulating tumor DNA • Metastases
    |
    TMB (Tumor Mutational Burden) • HRD (Homologous Recombination Deficiency)
    |
    AR mutation • AR amplification
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    3d
    Molecular Alterations in Paired Epithelial Ovarian Tumors in Patients Treated with Neoadjuvant Chemotherapy. (PubMed, Cancers (Basel))
    This study provides insights into the effect of NACT on the tumor molecular landscape. While BRCA1/2 and HRD status remained stable, an increase in TIL proportion and changes in the mutational profiles were observed post-treatment.
    Journal • Tumor mutational burden • BRCA Biomarker
    |
    TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
    |
    BRCA2 mutation • BRCA1 mutation • HRD
    3d
    KEYNOTE-E64: Phase 1a and Phase 2 Study for Safety, Preliminary Efficacy, PK and PD of ST-067 (clinicaltrials.gov)
    P1/2, N=316, Recruiting, Simcha IL-18, Inc. | Active, not recruiting --> Recruiting | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Jun 2025
    Enrollment open • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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    ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
    |
    TMB-H • MSI-H/dMMR • ALK positive • ALK mutation
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    Keytruda (pembrolizumab) • Gazyva (obinutuzumab) • vevoctadekin (ST-067)
    3d
    The potential of ESCO2 as a prognostic and immunotherapeutic marker of pan-cancer and its role in anti-PD1 treatment of bladder cancer. (PubMed, Oncology)
    Conclusion ESCO2 participates in regulating the immune infiltration and affecting the prognosis of patients in many cancers, especially in BLCA. ESCO2 may serve as a prognostic and immunotherapy biomarker in future treatment of human cancer.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Pan tumor
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    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ESCO2 (Establishment Of Sister Chromatid Cohesion N-Acetyltransferase 2)
    3d
    Testing the Combination of New Anti-cancer Drug Peposertib With Avelumab and Radiation Therapy for Advanced/Metastatic Solid Tumors and Hepatobiliary Malignancies (clinicaltrials.gov)
    P1/2, N=101, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • Combination therapy • Tumor mutational burden • IO biomarker • Metastases
    |
    TMB (Tumor Mutational Burden)
    |
    Bavencio (avelumab) • peposertib (M3814)
    3d
    Single-cell and bulk transcriptomic datasets enable the development of prognostic models based on dynamic changes in the tumor immune microenvironment in patients with hepatocellular carcinoma and portal vein tumor thrombus. (PubMed, Front Immunol)
    In vitro experiments were used to partially validate the biological prediction results. These results offer new insight into the biological and immunological landscape of PVTT in HCC patients, By utilizing individual patient risk scores, providing an opportunity to guide more effective immunotherapeutic interventional efforts.
    Journal • Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
    3d
    Cuproptosis-related lncRNAs emerge as a novel signature for predicting prognosis in prostate carcinoma and functional experimental validation. (PubMed, Front Immunol)
    Building on the three ClncRNAs, we identified a novel prognostic signature of PCa. The ClncRNA SNHG9 can promote PCa cell proliferation, migration, and invasion.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • FDX1 (Ferredoxin 1)
    3d
    Genomic alterations associated with early-stage disease and early recurrence in patients with colorectal cancer. (PubMed, Oncologist)
    Early-stage CRC patients can have distinct genomic profiles and CGP in this population can help expand access to targeted therapies.
    Journal • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker
    |
    BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • RNF43 (Ring Finger Protein 43)
    |
    BRAF V600E • MSI-H/dMMR • BRAF V600 • RNF43 mutation
    |
    FoundationOne® CDx
    3d
    LRP1B associated with immune cell infiltration influenced the efficacy of immunotherapy in colorectal cancer patients. (PubMed, Clinics (Sao Paulo))
    The authors described the molecular characteristics of CRC. Loss of LRP1B leads to changes in immune cell infiltration and can be used as a therapeutic target for colorectal cancer.
    Journal • Tumor mutational burden • IO biomarker • Immune cell
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • LRP1B (LDL Receptor Related Protein 1B) • MUC16 (Mucin 16, Cell Surface Associated) • TTN (Titin) • FAT4 (FAT Atypical Cadherin 4) • SYNE1 (Spectrin Repeat Containing Nuclear Envelope Protein 1) • ZFHX4 (Zinc Finger Homeobox 4)
    |
    TP53 mutation • KRAS mutation • APC mutation
    3d
    Genomic landscape of superficial malignant peripheral nerve sheath tumor. (PubMed, Lab Invest)
    Next-generation sequencing revealed multiple differential features between SF- MPNST, D-MPNST, SCM, and DM, including tumor mutation burden, mutational signatures, and differentially expressed genes. These findings help advance our understanding of disease pathogenesis and improve diagnostic modalities.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • PRAME (Preferentially Expressed Antigen In Melanoma) • MLPH (Melanophilin) • SOX11 (SRY-Box Transcription Factor 11) • CALB2 (Calbindin 2) • SOX8 (SRY-Box Transcription Factor 8)
    5d
    Reporting the Discrete Data of Four NGS Panels into the EHR System: A Single-Institute Experience (AMP 2024)
    Since its initial proposal in December of 2022, discrete reporting at the University of California, San Diego genomic lab was an effort that took close to a year-and-a-half to accomplish. Although the process was not without its hardships, the decision to go with an in-house approach saved the lab both time and resources compared to an outside approach. By exploring the capabilities and functionalities of its current laboratory information systems and EHR systems, the lab built a discrete reporting system that is effective for its needs as well as a framework for converting other and future NGS assays to discrete reporting.
    Next-generation sequencing • Tumor mutational burden
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    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
    |
    TruSight Oncology 500 Assay • Oncomine Precision Assay
    5d
    Analytical Performance of the New Illumina TruSight Oncology 500 V2 Assay for Comprehensive Genomic Profiling (AMP 2024)
    The new Illumina TSO500 v2 assay features a simplified workflow with improved performance and reduced turnaround time. Driven by innovations in assay design and bioinformatics, these capabilities can accelerate the democratization of actionable cancer biomarker detection, from small variants and copy number variants to RNA variants and complex biomarker outputs like TMB, MSI, and GIS scores.
    Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency)
    |
    HRD
    |
    TruSight Oncology 500 Assay
    5d
    Comprehensive Evaluation of Copy Number Variation from Gene to Arm-Level Using Targeted Sequencing (AMP 2024)
    OCA Plus supports comprehensive detection of relevant copy number alterations in cancer FFPE samples. Combined with small variant profiling, detection of MSI, TMB, and HRD, OCA Plus facilitates comprehensive analysis of DNA structural changes in cancer that are relevant to precision oncology research.
    Tumor mutational burden • BRCA Biomarker
    |
    TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • HRD (Homologous Recombination Deficiency)
    |
    IDH1 mutation • HRD • IDH1 mutation + Chr del(1p) + Chr del(19q)
    |
    Oncomine™ Comprehensive Assay Plus
    5d
    A Pilot Evaluation of the Workflow and Performance Characteristics of the Illumina TruSight Oncology 500 ctDNA v2 Assay (AMP 2024)
    In this pilot study, the TSO500 ctDNA v2 provided workflow enhancements with decreased overall turnaround time compared to TSO500 ctDNA v1, as well as low DNA input requirement, excellent sensitivity, and high accuracy.
    Tumor mutational burden • Circulating tumor DNA
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
    |
    TruSight Oncology 500 Assay • TruSight Oncology 500 ctDNA v2
    5d
    Simplifying the AVENIO Tumor Tissue CGP Manual Workflow: Performance of HRD, TMB, and MSI Signature Detection (AMP 2024)
    As evidence for multi-biomarker and complex genomic signatures grows in precision oncology, molecular pathology labs must evolve their sequencing capabilities with the latest innovation. The new AVENIO Tumor Tissue CGP Kit V2 demonstrates high performance and incorporates faster workflows, higher throughput, improved bioinformatics algorithms, and successful incorporation of a new HRD signature.
    Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency)
    |
    HRD • HRD signature • High HRD score
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    AVENIO Tumor Tissue CGP Kit
    5d
    IDH1/2 Mutations in Lung Cancer: A Closer Look at Their Incidence, Origin, and Clinical Characteristics (AMP 2024)
    IDH1/2 mutations are identified in a small subset of NSCLCs. Our findings suggest that >25% of these mutations are hematopoietic in origin with important implications for diagnosis and management of these patients. Among those with mutations arising from the lung neoplasm, IDH1/2 mutations were primarily seen in conjunction with another driver and were subclonal in nature, suggesting patterns of clonal heterogeneity and evolution.
    Clinical • Tumor mutational burden
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    KRAS mutation • BRAF mutation • IDH wild-type • IDH1 R132 • IDH2 R140Q • IDH1 R132L • IDH2 R140 • IDH2 R172
    |
    MSK-IMPACT
    5d
    Evaluation of Ancestry-Associated Bias in Tumor Mutational Burden Calculation in the TruSight Oncology 500 Platform (AMP 2024)
    Because no significant bias was identified in this limited cohort, an ancestry-based calibration constant or normalization procedure cannot be systematically applied. However, the TMB calling algorithm used by TSO500 relies upon population databases. Therefore, the underlying variants and calculations used to determine TMB should be manually evaluated on a case-by-case basis, particularly for tumors with TMBs close to treatment thresholds in patients of ancestries underrepresented in population databases.
    Tumor mutational burden • IO Companion diagnostic • IO biomarker
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H
    |
    FoundationOne® CDx • TruSight Oncology 500 Assay
    5d
    Automation of the New Illumina TruSight Oncology 500 v2 Assay on the Hamilton Microlab NGS STAR MOA System (AMP 2024)
    The new TSO500 v2 assay with automated library prep on the NGS STAR MOA liquid handler was demonstrated to perform comparably to manual library prep and offers a high-throughput solution to enable comprehensive genomic profiling with a faster, more flexible workflow and easier-to-use reagent kit.
    Next-generation sequencing • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency)
    |
    HRD
    |
    TruSight Oncology 500 Assay
    5d
    Detection of Novel Fusion Events in Gastric Carcinoma Involving the ARHGAP Gene Family (AMP 2024)
    Our study documents novel fusions in MSS gastric carcinoma involving the ARHGAP family. Patients with these tumors usually lack eligibility for targeted therapies, such as those directed against HER2 and involving immune checkpoint inhibition, and could ultimately benefit from new treatment avenues modulating RHOA activity as a result of ARHGAP fusions.
    Tumor mutational burden • IO biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ARID1A (AT-rich interaction domain 1A) • CLDN18 (Claudin 18) • PBRM1 (Polybromo 1) • KMT2D (Lysine Methyltransferase 2D) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • KDM6A (Lysine Demethylase 6A) • RHOA (Ras homolog family member A) • SOX9 (SRY-Box Transcription Factor 9) • ELF3 (E74 Like ETS Transcription Factor 3) • ARHGAP • CDKN1B (Cyclin dependent kinase inhibitor 1B) • CTNND1 (Catenin Delta 1) • ARHGAP42 (Rho GTPase Activating Protein 42)
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    TMB-H • HER-2 amplification • PBRM1 mutation
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    MI Tumor Seek™
    5d
    Comparative Analysis of Variant Reporting and HRD Performance: Evaluating AVENIO Tumor Tissue CGP Automated Assay Against F1CDx Assay and PGDx elio Test (AMP 2024)
    The AVENIO CGP Assay demonstrated high agreement with 2 established CGP tests, F1CDx and PGDx, in variant reporting, and closely aligned with F1CDx in HRDsig analysis across various tissue types. These results highlight the assay's reliability and demonstrate its utility in translational research.
    Tumor mutational burden
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    HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • HRD (Homologous Recombination Deficiency)
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    HER-2 amplification • HRD • ALK rearrangement • RET rearrangement • HRD signature
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    FoundationOne® CDx • AVENIO Tumor Tissue CGP Kit • PGDx elio™ tissue complete assay
    5d
    Automation of the Illumina TruSight Oncology 500 ctDNA v2 Assay on the Hamilton Microlab NGS STAR MOA System (AMP 2024)
    The TSO500 ctDNA v2 assay with automated library prep on the NGS STAR MOA liquid handler has demonstrated performance comparable to manual library prep and offers a high-throughput solution to enable comprehensive genomic profiling with a faster chemistry, more flexible workflow, and easier-to-use reagent kit.
    Next-generation sequencing • Tumor mutational burden • Circulating tumor DNA
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    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
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    TruSight Oncology 500 Assay • TruSight Oncology 500 ctDNA v2
    5d
    Clinical Validation of an In-House-Developed Somatic Copy Number Calling Pipeline to Use on the TruSight Oncology 500 Next-Generation Sequencing (TSO500) Kit in Solid Tumors (AMP 2024)
    The OncCNV pipeline accurately detects GAMP, HMZ, and BI beyond the reportable range validated by Illumina. Development of the OncCNV pipeline further enhances the clinical utility of the TSO500 assay, as demonstrated in this cohort of solid tumor samples.
    Clinical • Next-generation sequencing • Tumor mutational burden
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    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
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    TruSight Oncology 500 Assay
    5d
    Comprehensive Genomic and Immune Profiling for the Detection of Clinically Significant Tumor Biomarkers (AMP 2024)
    Utilization of a multi-modal CGIP testing strategy resulted in a high rate of test success and detection of clinically relevant biomarkers and optimizing tissue usage.
    Clinical • Tumor mutational burden • IO Companion diagnostic • PD(L)-1 Biomarker • IO biomarker • PD(L)-1 companion diagnostic
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    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
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    PD-L1 expression • TMB-H
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    TruSight Oncology 500 Assay • Oncomine™ Immune Response Research Assay