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    TEST:
    MI Tumor Seek™

    Company:
    Caris Life Sci
    Type:
    Laboratory Developed Test
    Related tests:
    Details
    Evidence

    News

    18d
    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)
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    KRAS mutation • IDO1 expression • CTLA4 expression
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    MI Tumor Seek™
    19d
    Characterization and impact of non-canonical WNT signaling on outcomes of urothelial carcinoma. (PubMed, Cancer Med)
    Distinct genomic and immune landscapes for the four investigated WNT5A pathway components were observed in patients with UC. External validation studies are needed.
    Journal • IO biomarker
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    TP53 (Tumor protein P53) • FGFR3 (Fibroblast growth factor receptor 3) • RB1 (RB Transcriptional Corepressor 1) • ROR1 (Receptor Tyrosine Kinase Like Orphan Receptor 1) • ROR2 (Receptor Tyrosine Kinase Like Orphan Receptor 2) • WNT5A (Wnt Family Member 5A) • FZD2 (Frizzled Class Receptor 2)
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    WNT5A expression
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    MI Tumor Seek™
    1m
    Differences in genomic, transcriptomic and immune landscape of prostate cancer (PCa) based on site of metastasis (mets) (AUA 2024)
    This study highlights distinct molecular profiles in metastatic prostate cancer (PCa) based on metastasis site, underlining the importance of personalized treatment strategies. The findings, particularly the variations in gene mutations and AR signaling, are crucial in tailoring management approaches for advanced PCa.
    Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • 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) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • BAP1 (BRCA1 Associated Protein 1) • IFNG (Interferon, gamma) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • KMT2C (Lysine Methyltransferase 2C) • APC (APC Regulator Of WNT Signaling Pathway) • SPOP (Speckle Type BTB/POZ Protein)
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    TP53 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • PTEN mutation • BAP1 mutation • APC mutation • AR mutation • AR splice variant 7
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    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
    2ms
    The genomic, transcriptomic, and immunologic landscape of TEM8 (ANTXR1) in neuroendocrine neoplasms (NENs) (AACR 2024)
    The increased immune cell infiltrate and prevalence of T-cell inflamed status among ANTXR1H NENs suggests these tumors might be more responsive to treatment with ICIs. As trials incorporating intratumoral injections of SVV-01 in combination with ICIs are underway, further investigation of clinical and molecular associations with ANTXR1 expression in NENs is warranted.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • ANTXR1 (ANTXR Cell Adhesion Molecule 1)
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    PD-L1 expression • TMB-H
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    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
    2ms
    Describing the molecular landscape of cervical cancer metastases: Implications for future therapeutic targets (AACR 2024)
    Hierarchical clustering of CCM sites by alterations (mutations, amplifications and fusions) frequency revealed CCM to Liver (n=77) and Lymph Nodes (n=265) as the most distinct from CCP while Vagina/Vulva (V/V) (n=196) and Lung (n=115) CCM were most similar. Lymph Nodes had decreased TP53-mt (6.6% vs 14.7%) and ARID1A-mt (4.53% vs 8.27%) but higher BRCA1-mt (3.03% vs 0.87%) compared to CCP (p<0.05). Liver had higher BRCA1-mt (6.67% vs 0.87%), ASXL1-mt (8.47% vs 2.96%) and APC-mt (4% vs 0.65%) compared to CCP (p<0.05).
    Tumor mutational burden • PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • ARID1A (AT-rich interaction domain 1A) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • ASXL1 (ASXL Transcriptional Regulator 1) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • PD-L2 (Programmed Cell Death 1 Ligand 2) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule)
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    CTLA4 expression
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    PD-L1 IHC 22C3 pharmDx • MI Tumor Seek™
    2ms
    Evidence for Unified Assessment Criteria of HER2 IHC in Colorectal Carcinoma (USCAP 2024)
    CRCs that were HER2/Het+ were invariably ISH positive, while NGS was not as sensitive for HER2 amplification in this subgroup. Our results suggest that ISH is likely unnecessary for CRC with 3+ HER2 overexpression in 10-49% of tumor cells, and that NGS has suboptimal sensitivity for this cohort.
    HER-2 (Human epidermal growth factor receptor 2)
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    HER-2 overexpression • RAS wild-type
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    PATHWAY antiHer2/neu (4B5) Rabbit Monoclonal Primary Antibody • MI Tumor Seek™
    2ms
    EWSR1::CREM Fusion: A New Finding in Thoracic and Head/Neck Squamous Cell Carcinoma (USCAP 2024)
    Our study broadens the spectrum of tumors associated with EWSR1::CREM rearrangement and is the first to document its presence in SCCs of the lung and head and neck. While there is no specific standardized approach to treatment for patients whose tumors have these translocations, it is noteworthy that all three patients in this series are alive despite the presence of metastases and, in some instances, the absence of therapy over several years. Identification of additional cases will be helpful to better understand the disease course and optimal therapy of SCC harboring the EWSR1::CREM fusion.
    EWSR1 (EWS RNA Binding Protein 1) • FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor) • TP63 (Tumor protein 63) • CREM (CAMP Responsive Element Modulator)
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    MI Tumor Seek™
    3ms
    Molecular characterization of squamous cell ovarian cancers for identification of therapeutic targets (SGO 2024)
    OSCC tumors were more likely to be TMB-H compared to BT and HGSOC, with increased mutational prevalence in multiple genes like PIK3CA, FBXW7, CDKN2A, FAT1, pTERT but no ER or PR positivity. Additionally, OSCC tumors also had increased expression of many IC genes, infiltration of M1 Macrophages and higher T-cell inflamed frequency. One limitation of this study is the small sample size of OSCC compared to HGSOC, but further characterization of this rare histological subtype with a poor prognosis may lead to identification of therapeutic targets.
    Tumor mutational burden • PD(L)-1 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) • PGR (Progesterone receptor) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • KMT2D (Lysine Methyltransferase 2D) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • PD-L2 (Programmed Cell Death 1 Ligand 2) • FAT1 (FAT atypical cadherin 1) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule)
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    TP53 mutation • TMB-H • PIK3CA mutation
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    PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
    4ms
    Survival outcomes according to molecular classification of uterine carcinosarcoma (SGO 2024)
    As expected, CNH/TP53 MT is the most common molecular subtype in this studied population. There is tiered survival between UCS sub-types, which mirrors EEC survival patterns. Despite UCS being considered a more aggressive histology, POLE MT and MSI-H have equivalent outcomes when comparing UCS and EEC, but CNL/TP53 WT and CNH/TP53 MT have worse outcomes in the UCS cohort compared to the EEC cohort.
    Tumor mutational burden • MSi-H Biomarker
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    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
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    TMB-H • MSI-H/dMMR • TP53 wild-type
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    MI Tumor Seek™
    4ms
    Molecular Characterization of TFE3-rearranged Renal Cell Carcinoma, A Comparative Study with Papillary and Clear Cell Renal Cell Carcinomas. (PubMed)
    Gene set enrichment analysis showed rRCC are enriched in genes related to oxidative phosphorylation when compared to both ccRCC and pRCC. Despite having a relatively cold TME compared to pRCC and ccRCC, increased PDL1+ rates in rRCC suggest a potential benefit from immune checkpoint inhibitor (ICI) therapy.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    MI Tumor Seek™
    4ms
    IL-6 and PIM1 expression in renal cell carcinoma. (ASCO-GU 2024)
    In RCC cell lines, IL-6 blockade through either anti-IL-6 antibody or tocilizumab was sufficient to decrease PIM1 protein levels. Treatment with ruxolitinib leads to a dose and time-dependent decrease in PIM1 levels... These results suggest that differential expression of PIM1 in RCC may be linked to autocrine IL-6 signaling. Furthermore, poor survival in PIM1-overexpressing RCC patients is independent of treatment received, and therefore necessitates use of targeted therapies against this axis. Multiple FDA-approved agents are available that target this pathway.
    IL6 (Interleukin 6) • PIM1 (Pim-1 Proto-Oncogene)
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    IL6 expression • PIM1 overexpression
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    MI Tumor Seek™
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    Jakafi (ruxolitinib) • Actemra IV (tocilizumab)
    4ms
    Canonical Wnt signaling pathway (WSP) alterations in metastatic prostate cancer. (ASCO-GU 2024)
    WSP-act prostate cancer demonstrated a pronounced upregulation of ROR1 gene expression, underscoring its potential involvement in the crosstalk between the canonical and non-canonical Wnt signaling pathways. Additionally, the augmented levels of M2 macrophages in WSP-act tumors, combined with the reported role of ROR1 in tumor immunosuppression, suggests that ROR1 may contribute to immune evasion in WSP-act mPCa. Our findings may provide rationale for developing novel therapeutic strategies targeting Wnt-activated prostate cancers.
    MSi-H Biomarker • Metastases
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    RNF43 (Ring Finger Protein 43) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • ROR1 (Receptor Tyrosine Kinase Like Orphan Receptor 1) • SPOP (Speckle Type BTB/POZ Protein) • RSPO2 (R-Spondin 2)
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    MSI-H/dMMR • ROR1 expression • RNF43 mutation • SPOP mutation • RNF43 G659fs • CTNNB1 expression
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    MI Tumor Seek™
    4ms
    The opposing effects of Class 1B and Class 2 FOXA1 mutations in prostate cancer. (ASCO-GU 2024)
    Different FOXA1 alterations exhibit divergent molecular and clinical features, and should not be interpreted in aggregate. In particular, Class 1B mutations are associated with a unique molecular and immunological landscape with potentially better outcomes to ADT, while Class 2 mutations are associated with NEPC phenotype with inferior ADT sensitivity.
    MSi-H Biomarker
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    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CD276 (CD276 Molecule) • ERG (ETS Transcription Factor ERG) • FOXA1 (Forkhead Box A1) • TMPRSS2 (Transmembrane serine protease 2)
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    TP53 mutation • TMB-H • MSI-H/dMMR • TMPRSS2-ERG fusion • FOXA1 mutation
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    MI Tumor Seek™
    4ms
    Differences in genomic, transcriptomic, and immune landscape of prostate cancer (PCa) based on site of metastasis (mets). (ASCO-GU 2024)
    We elucidate molecular and immunologic mechanisms of metastatic tropism in advanced PCa. These data may facilitate future drug development.
    Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • 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) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • BAP1 (BRCA1 Associated Protein 1) • IFNG (Interferon, gamma) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • KMT2C (Lysine Methyltransferase 2C) • APC (APC Regulator Of WNT Signaling Pathway) • SPOP (Speckle Type BTB/POZ Protein)
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    TP53 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • PTEN mutation • BAP1 mutation • APC mutation • AR splice variant 7
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    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
    5ms
    Association of class II and III BRAF mutations with EGFR blockade therapy response and representation of molecularly distinct subgroups of BRAF mutations in MMR proficient CRC. (ASCO-GI 2024)
    "Class I BRAF mts (V600) render aggressive biology to CRC and poor response to anti EGFR inhibitors... Class II and III BRAF mts are associated with improved outcomes with EGFR blockade and represent a distinct biological subgroup of pMMR CRC. Class III BRAF mts have lower MAPK activation, consistent with the pattern of kinase-dead mutations."
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IFNG (Interferon, gamma)
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    EGFR mutation • BRAF mutation • BRAF V600 • BRAF wild-type
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    MI Tumor Seek™
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    EGFR bi-armed autologous activated T cells
    5ms
    Characterization of the cachexia pathway in pancreatic ductal adenocarcinoma. (ASCO-GI 2024)
    This is the largest molecular and clinical characterization of the myostatin-activin cachexia pathway in PDAC. Our data show that increased activation of the myostatin-activin pathway is associated with immune mediators, lipid metabolism, and inflammatory gene activation. Activators and repressors are significant predictors of survival in PDAC, suggesting possible novel therapeutic targets.
    PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • STK11 (Serine/threonine kinase 11) • ARID1A (AT-rich interaction domain 1A) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • SMAD4 (SMAD family member 4) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CCL2 (Chemokine (C-C motif) ligand 2) • IL1B (Interleukin 1, beta) • SMAD7 (SMAD Family Member 7) • ACVR2A (Activin A Receptor Type 2A) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule) • SMAD2 (SMAD Family Member 2) • SMAD3 (SMAD Family Member 3) • SMURF1 (SMAD Specific E3 Ubiquitin Protein Ligase 1) • SMURF2 (SMAD Specific E3 Ubiquitin Protein Ligase 2) • TGFBR1 (Transforming Growth Factor Beta Receptor 1) • ACVR1B (Activin A Receptor Type 1B) • ACVR2B (Activin A Receptor Type 2B)
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    PD-L1 expression • TP53 mutation • KRAS mutation • TMB-H • MSI-H/dMMR • ARID1A mutation • STK11 mutation
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    MI Tumor Seek™
    5ms
    Genomics and transcriptomics of pancreatic adenosquamous carcinoma. (ASCO-GI 2024)
    This is the largest molecular profiling analysis of PASC, which is characterized by unique genomic alterations, and is associated with higher PD-L1 expression, immune related gene expression, CD4+ T cell infiltration and IFN gamma signature, and lower MAPK activation. PASC is associated with better OS compared to PSCC. These findings may provide subtype-specific therapeutic opportunities for PASC and PSCC pts.
    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) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • SF3B1 (Splicing Factor 3b Subunit 1) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CD4 (CD4 Molecule) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • CASP8 (Caspase 8) • HMGA2 (High mobility group AT-hook 2) • AXIN1 (Axin 1) • CDKN1B (Cyclin dependent kinase inhibitor 1B) • BCL9 (BCL9 Transcription Coactivator) • ZNF384 (Zinc Finger Protein 384)
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    PD-L1 expression • TMB-H • MSI-H/dMMR • PTEN mutation • ROS1 fusion • SF3B1 mutation • CTLA4 expression • AKT2 amplification • CD4 expression
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    MI Tumor Seek™
    5ms
    Molecular and immune landscape by cyclin dependent kinase (CDK) 4/6 expression and TP53 mutational status in mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). (ASCO-GI 2024)
    Our comprehensive analysis is the first to show distinct mutational profiles according to TP53 mut status, and differential expression of immune-related genes and TME cell infiltration independent of TP53 mut in CDK4/6 high vs low dMMR/MSI-H CRC. In our series, CDK6 expression correlated with ICI treatment benefit in TP53 mut tumors, warranting further studies to explore the potential of targeting the CDK4/6 axis to enhance ICI efficacy in CRC.
    Microsatellite instability • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker • Mismatch repair
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    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MSI (Microsatellite instability) • DNMT3A (DNA methyltransferase 1) • ARID1A (AT-rich interaction domain 1A) • PD-1 (Programmed cell death 1) • KMT2A (Lysine Methyltransferase 2A) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • CDH1 (Cadherin 1) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • FANCL (FA Complementation Group L) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule) • HNF1A (HNF1 Homeobox A)
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    TP53 mutation • KRAS mutation • MSI-H/dMMR • BRAF mutation • ARID1A mutation • DNMT3A mutation • APC mutation • NF2 mutation • TP53 expression • MLL mutation • CDK4 mutation • CDK6 expression
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    MI Tumor Seek™
    5ms
    APC as a high-utility mutational biomarker that may identify subpopulations of patients with mutant RAS/BRAF and right-sided colorectal cancer (CRC) who derive benefit from EGFR inhibitors (EGFRi). (ASCO-GI 2024)
    Sponsored by NCI, NCI Background: Although, EGFRi including Cetuximab (CTX) and Panitumumab (PMB) is restricted to KRAS wild-type (KRASWT) tumors, ~50% of patients still fail to respond to therapy. Our data suggests that the simple application of a high-utility mutational biomarker (APC), may increase the eligibility for successful EGFRi therapy in a substantial subpopulation of RAS/BRAF mt patients as well as right-sided CRC, potentially altering the standard of care. Further validation of this biomarker in a prospective clinical trial is warranted. >
    Clinical
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog)
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    TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • NRAS mutation • KRAS wild-type • BRAF wild-type • RAS mutation • RAS wild-type • APC mutation • RAS wild-type + BRAF wild-type
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    MI Tumor Seek™
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    Erbitux (cetuximab) • Vectibix (panitumumab)
    5ms
    High-resolution transcriptional signature to predict survival benefit in colorectal cancer (CRC) treated with EGFR inhibitors (EGFRi) independent of RAS/BRAF mutation status or tumor sidedness. (ASCO-GI 2024)
    Sponsored by NCI, NCI Background: Cetuximab (CTX) and Panitumumab (PMB) therapies directed at EGFR have been restricted to left-sided CRC harboring wild-type KRAS (KRASWT), limiting their utility. Our data suggest that CTX-S may predict longer survival on EGFRi, surprisingly independent of RAS/BRAF mutation status as well as tumor sidedness. Patients with high CTX-S had increased prevalence of CMS2 and harbored more APC and TP53 mutations. A strong EGFRi biomarker would likely expand the utility of EGFRi to right-sided tumors and possibly to RASMUT tumors.
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • APC (APC Regulator Of WNT Signaling Pathway) • RAS (Rat Sarcoma Virus)
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    TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • NRAS mutation • KRAS wild-type • BRAF wild-type • RAS mutation • RAS wild-type • APC mutation • RAS wild-type + BRAF wild-type • RNF43 mutation
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    MI Tumor Seek™
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    Erbitux (cetuximab) • Vectibix (panitumumab)
    6ms
    Genomic Landscape of Malignant Phyllodes Tumors Identifies Subsets for Targeted Therapy (SABCS 2023)
    Additionally, one MPT sample harbored a pathogenic NTRK1 fusion (TPM4:NTRK1), and treatment with larotrectinib for over 16 months suggests a clinical response to therapy... Our study demonstrates the importance of employing next generation sequencing (NGS) in MPTs to detect actionable genomic alterations. To effectively analyze fusions, an NGS panel that include RNA sequencing is recommended, considering the occurrence of NTRK1 fusion reported herein. Although HER2 transcriptional expression was low, further investigations examining HER2 IHC in PTs are still necessary.
    Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • KMT2D (Lysine Methyltransferase 2D) • TPM4 (Tropomyosin 4)
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    PD-L1 expression • EGFR mutation • MSI-H/dMMR • BRAF mutation • HER-2 negative • PIK3CA mutation • NTRK1 fusion • HER-2 expression • NF1 mutation • KMT2D mutation
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    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
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    Vitrakvi (larotrectinib)
    6ms
    Comprehensive Molecular and Immunological Characterization of Invasive Ductal Triple-Negative Breast Cancer (SABCS 2023)
    ID TNBC was associated with worse OS compared to ID non-TNBC (mOS: 24.5 vs 54.6 months; HR: 0.5, 95% CI 0.47-0.57; p < 0.00001) but trend towards better survival with pembrolizumab (mOS: 29.4 vs 8.8 month; HR: 0.67, 95% CI 0.28-1.5; p=0.3) treatment... These data indicate that ID TNBC is associated with distinct mutational profile compared to non-TNBC, has increased T cell inflamed score, IFNy score, MHC class I and immune checkpoint gene expression, and differential immune cell infiltration. Interestingly, TNBC was associated with increased M1 and decreased M2M. There is evidence to suggest that transcriptomically defined M1 high tumors are clinically aggressive and have worse OS in TNBC.
    PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BCL2 (B-cell CLL/lymphoma 2) • HRAS (Harvey rat sarcoma viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • NF1 (Neurofibromin 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CCNE1 (Cyclin E1) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein) • PD-L2 (Programmed Cell Death 1 Ligand 2) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • BCL2L11 (BCL2 Like 11) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • BCL2A1 (BCL2 Related Protein A1) • BCL2L2 (BCL2 Like 2) • HLA-B (Major Histocompatibility Complex, Class I, B) • FANCI (FA Complementation Group I) • FOXP3 (Forkhead Box P3) • NFIB (Nuclear Factor I B) • PMAIP1 (Phorbol-12-Myristate-13-Acetate-Induced Protein 1) • BCL2L10 (BCL2 like 10) • TAP1 (Transporter 1) • BAK1 (BCL2 Antagonist/Killer 1) • BBC3 (BCL2 Binding Component 3)
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    PD-L1 expression • EGFR mutation • HRAS mutation • BCL2 expression • MCL1 expression
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    PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
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    Keytruda (pembrolizumab)
    6ms
    Multi-omic Characterization and Molecular Profiling of NUT Carcinoma (AMP 2023)
    NRG1 fusion events are infrequently observed in ovarian, fallopian tube, and primary peritoneal carcinomas, and include a diversity of previously unknown partner genes. However, they may carry diagnostic significance in the context of borderline/low-grade serous tumors and have important therapeutic implications with the emergence of new targeted treatments.
    Tumor mutational burden • BRCA Biomarker
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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) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • FGFR3 (Fibroblast growth factor receptor 3) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ARID1A (AT-rich interaction domain 1A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NRG1 (Neuregulin 1) • KMT2D (Lysine Methyltransferase 2D) • CDK12 (Cyclin dependent kinase 12) • MUC16 (Mucin 16, Cell Surface Associated) • NOTCH2 (Notch 2) • CHEK2 (Checkpoint kinase 2) • ADAM9 (ADAM Metallopeptidase Domain 9) • EP300 (E1A binding protein p300) • RAD51D (RAD51 paralog D) • WRN (WRN RecQ Like Helicase) • IR (Insulin receptor) • FANCE (FA Complementation Group E) • JAG1 (Jagged Canonical Notch Ligand 1) • CXADR (CXADR Ig-Like Cell Adhesion Molecule) • FANCC (FA Complementation Group C) • TMEM65 (Transmembrane Protein 65) • TNFRSF12A (TNF Receptor Superfamily Member 12A)
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    NRG1 fusion • NRG1 fusion
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    MI Tumor Seek™
    6ms
    Detection of NRG1 Fusion Events in Ovarian, Fallopian Tube, and Primary Peritoneal Carcinomas (AMP 2023)
    This large patient cohort demonstrates that NC is characterized by NUTM1 gene fusions, low mutational burden, and general lack of additional oncogenic drivers. The prognosis of NCs remains dismal, and future work could focus on subpopulations of immune cell-rich tumors that might be responsive to immunotherapy.
    Tumor mutational burden • IO biomarker
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    TMB (Tumor Mutational Burden) • NRG1 (Neuregulin 1) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • KDM6A (Lysine Demethylase 6A) • NSD3 (Nuclear Receptor Binding SET Domain Protein 3) • BRD4 (Bromodomain Containing 4) • NUTM1 (NUT Midline Carcinoma Family Member 1) • BRD3 (Bromodomain Containing 3)
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    TMB-L • NRG1 fusion • NRG1 fusion
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    MI Tumor Seek™
    7ms
    Characterizing the role of NSD family of histone methyltransferases in the head and neck squamous cell carcinoma tumor immune microenvironment (ESMO Asia 2023)
    Conclusions Our data suggest a strong association between NSD expression and increased M2 MΦ, Tregs, T cell inflamed score and immune regulatory genes. A better understanding of these differences will provide a rationale for tailored therapeutic approaches for NSD-expressing HNSCC.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Epigenetic controller
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    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • PD-1 (Programmed cell death 1) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • PD-L2 (Programmed Cell Death 1 Ligand 2) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • NSD3 (Nuclear Receptor Binding SET Domain Protein 3) • FOXP3 (Forkhead Box P3) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
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    FOXP3 expression
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    MI Tumor Seek™
    7ms
    Characterizing somatostatin receptor 2 (SSTR2) expression and the immune landscape of olfactory neuroblastoma (ONB), sinonasal neuroendocrine carcinoma (SNEC), and sinonasal undifferentiated carcinoma (SNUC) (SITC 2023)
    101 (b), this study was performed utilizing retrospective, deidentified clinical data. Therefore, this study was deemed Institutional Review Board exempt, and no patient consent was necessary from the subjects.
    PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • SSTR (Somatostatin Receptor) • SSTR2 (Somatostatin Receptor 2)
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    PD-L1 expression • MSI-H/dMMR • SSTR2 expression
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    PD-L1 IHC 22C3 pharmDx • MI Tumor Seek™
    7ms
    Analyzing the genomic, transcriptomic and immune landscapes associated with surface somatostatin receptor 2 (SSTR2) gene expression in nasopharyngeal carcinoma (NPC) (SITC 2023)
    Recurrent and metastatic NPC is treated with cisplatin-based chemotherapy regimens, with poor survival...Thus, in SSTR2-H NPC, immunotherapy and also SSTR2-directed strategies may be appropriate therapeutic strategies. In EBV- NPC, PIK3CA-directed therapy merits further investigation.
    PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • SSTR (Somatostatin Receptor) • SSTR2 (Somatostatin Receptor 2)
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    PD-L1 expression • MSI-H/dMMR • PIK3CA mutation • SSTR2 expression
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    PD-L1 IHC 22C3 pharmDx • MI Tumor Seek™
    |
    cisplatin
    7ms
    MI tumor Seek Hybridâ„¢, a Novel Combined WES and WTS Molecular Profiling Assay with a Single Extraction and Sequencing Workflow (AMP 2023)
    By simultaneously capturing DNA and RNA, MI Tumor Seek Hybridâ„¢ provides a comprehensive molecular blueprint that saves tissue without compromising results and delivers transformative value across the healthcare ecosystem. Join us to learn about MI tumor Seek Hybridâ„¢ and how it can help guide treatment decisions and improve patient outcomes.
    MI Tumor Seek™
    7ms
    Impact of gender and mutational differences in hormone receptor expressing non-small cell lung cancer. (PubMed, Front Oncol)
    Women were more likely to have HR+ NSCLC than men and EGFR and KRAS mutations occurred more commonly in HR+ NSCLC. Additional studies with more strict inclusion criteria for HR+ are warranted to see if there is benefit to targeting HR in these subgroups.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PGR (Progesterone receptor)
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    TP53 mutation • KRAS mutation • EGFR mutation • EGFR mutation + KRAS mutation
    |
    MI Tumor Seek™
    8ms
    Concurrent predictors of an immune responsive tumor microenvironment within tumor mutational burden-high breast cancer. (PubMed, Front Oncol)
    Along with MSI-H and PD-L1+, several biomarkers, including B2M mutation and CD274 amplification, may help predict ICI benefit amongst TMB-H tumors. Co-occurring biomarkers within TMB-H breast cancer warrant evaluation in larger cohorts for response or resistance to ICI to develop composite predictive biomarkers in MBC.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • B2M (Beta-2-microglobulin) • CDH1 (Cadherin 1)
    |
    PD-L1 expression • TMB-H • MSI-H/dMMR • HER-2 negative • HER-2 mutation • TMB-L • PD-L1 amplification • B2M mutation • CDH1 mutation
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    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
    8ms
    MOLECULAR LANDSCAPE OF ENDOMETRIAL STROMAL SARCOMA IN A LARGE REAL-WORLD PATIENT COHORT (CTOS 2023)
    This series represents the largest cohort of multi-omic characterization of ESS. Our data confirmed the characteristic presence of JAZF1:SUZ12 fusions in LG-ESS. However, this fusion was also found in HG-ESS cases with retention of ER and PR expression.
    Real-world evidence • Clinical • Tumor mutational burden • MSi-H Biomarker • Real-world • Stroma
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    ER (Estrogen receptor) • TP53 (Tumor protein P53) • PGR (Progesterone receptor) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler) • BCOR (BCL6 Corepressor) • NUTM2B (NUT Family Member 2B) • HMGA2 (High mobility group AT-hook 2) • JAZF1 (JAZF Zinc Finger 1) • LRIG3 (Leucine-rich repeats and immunoglobulin-like domains protein 3) • SUZ12 (SUZ12 Polycomb Repressive Complex 2 Subunit)
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    TP53 mutation • TMB-H • MSI-H/dMMR • ER positive + PGR positive • ATRX mutation • PGR positive • BCOR mutation • PGR expression
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    MI Tumor Seek™
    8ms
    OVEREXPRESSION OF CYCLIN DEPENDENT KINASES AND CYCLINS ACROSS SARCOMAS BEYOND CDK4 (CTOS 2023)
    We identified overexpressers of CDK and cyclin genes among a heterogeneous sample of sarcoma patients. By setting a threshold of 2 SD above the mean of each gene we captured the top ~2% of expressers, and by considering subtypes with ≥ 25% of cases above that threshold we accurately identified known associations between CDK4/LPS and CCND1/Ewing sarcoma while also revealing new associations. The most notable overexpressers were chordoma (CDK7, CDK18), CCS (CDK2, CCNA1), RCS (CCND2), and RMS (CDK6, CDK8, CCND2, CCNE1).
    CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • CCND2 (Cyclin D2) • CDK2 (Cyclin-dependent kinase 2) • CDK7 (Cyclin Dependent Kinase 7) • CDK9 (Cyclin Dependent Kinase 9) • CCNA1 (Cyclin A1)
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    CCNE1 overexpression • CDK4 amplification • CCND1 overexpression • CDK4 overexpression • CDK2 overexpression • CDK6 overexpression • CCND2 overexpression • PPP3CA expression
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    MI Tumor Seek™
    9ms
    STAT3, ACTA2, and SPARC stromal markers predict response to Gemcitabine/Cisplatin/Nab-paclitaxel (GCN) in patients with advanced pancreatic adenocarcinoma (apdac) (ESMO 2023)
    In patients who received GN, MMP-2 was associated with better outcome. Analysis of stromal markers STAT3, ACTA2, and SPARC in a prospective trial is ongoing.
    Clinical • BRCA Biomarker • Stroma • Metastases
    |
    IL6 (Interleukin 6) • BRCA (Breast cancer early onset) • STAT3 (Signal Transducer And Activator Of Transcription 3) • ACTA2 (Actin Alpha 2 Smooth Muscle) • MMP2 (Matrix metallopeptidase 2) • TGFB1 (Transforming Growth Factor Beta 1) • STAT2 (Signal transducer and activator of transcription 2) • TGFB2 (Transforming Growth Factor Beta 2)
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    STAT3 expression
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    MI Tumor Seek™
    |
    cisplatin • gemcitabine • albumin-bound paclitaxel
    9ms
    Landscape of Delta-like-ligand 3 (DLL3) expression across neuroendocrine neoplasms (NENs) (ESMO 2023)
    Conclusions High DLL3 expression is associated with poor overall survival, advanced pathologic grade, and distinct immune landscape. Further development of DLL3-targeted therapies for high-grade NENs is warranted.
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • RB1 (RB Transcriptional Corepressor 1) • DLL3 (Delta Like Canonical Notch Ligand 3) • ASCL1 (Achaete-Scute Family BHLH Transcription Factor 1)
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    TMB-H • DLL3 expression • DLL3 overexpression
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    MI Tumor Seek™
    9ms
    Therapeutic opportunities for porcupine inhibition in gastrointestinal cancer (ESMO 2023)
    Preclinically, GI tumors with upstream Wnt pathway variants (RNF43 loss of function (LoF), RSPO gain of function (GoF)) are Wnt ligand dependent and exquisitely sensitive to RXC004, a small molecule Porcupine inhibitor...Conclusions Upstream Wnt pathway variants are enriched in GI cancer, in particular Small Bowel cancer, a rare subtype of high unmet need. In MSS CRC cancer, the poor prognosis and high BRAF_V600E co-occurrence with upstream Wnt pathway variants suggests benefit of co-targeting Wnt and MAPK pathways in this population.
    RNF43 (Ring Finger Protein 43) • RSPO2 (R-Spondin 2) • RSPO3 (R-Spondin 3)
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    BRAF V600E • BRAF V600 • BRAF wild-type
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    MI Tumor Seek™
    |
    zamaporvint (RXC004)
    9ms
    Characterization of MET Exon 14 Skipping Analog (Y1003) in Non-Small Cell Lung Cancer (NSCLC) (IASLC-WCLC 2023)
    We present the largest molecular analysis of Y1003 mutations along with a comparison against METex14. Like METex14, Y1003 was associated with MDM2 and CDK4 co-amplifications and increased expression of IDO1, potential therapeutic targets. Y1003 was also associated with a highly immunogenic tumor microenvironment.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • STK11 (Serine/threonine kinase 11) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • PD-L2 (Programmed Cell Death 1 Ligand 2) • IDO1 (Indoleamine 2,3-dioxygenase 1)
    |
    TMB-H • MET exon 14 mutation • MET expression • CDK4 amplification • IDO1 expression
    |
    PD-L1 IHC 22C3 pharmDx • MI Tumor Seek™
    9ms
    Molecular Characteristics of Non-Small Cell Lung Cancer with MET Fusions (IASLC-WCLC 2023)
    MET fusions are a rare, but potentially actionable, genomic alteration. Our study provides a comprehensive characterization of MET fusions in NSCLC, revealing their diverse fusion partners and co-occurring genomic alterations. Further research is warranted to elucidate the clinical implications of MET fusions in the treatment of various types of cancer, including lung cancer.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • KIF5B (Kinesin Family Member 5B) • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • GPRC5C (G Protein-Coupled Receptor Class C Group 5 Member C)
    |
    PD-L1 expression • BRAF V600E • KRAS mutation • EGFR mutation • TMB-H • PD-L1 overexpression • BRAF V600 • EGFR L858R • MET amplification • RET fusion • MET exon 14 mutation • EGFR mutation + KRAS mutation • BRAF L597Q • MET fusion • EGFR E746 • KRAS Q61L • PD-L1-L • BRAF L597
    |
    PD-L1 IHC 22C3 pharmDx • FusionPlex® Dx • MI Tumor Seek™
    9ms
    Molecular Characterization of Non-small Cell Lung Cancer in People Living with HIV or Solid Organ Transplants (IASLC-WCLC 2023)
    The identification of targetable genomic alterations in tumors from individuals living with HIV and solid organ transplant recipients underscores the importance of comprehensive molecular testing in these patient populations. While important markers of immunotherapy response (PD-L1, TMB) were similar, different immune characteristics were identified. Further research is necessary to fully understand the molecular profiles of lung cancer in individuals with HIV and solid organ transplant.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    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) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • KDM5C (Lysine Demethylase 5C)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • TMB-H • KRAS G12C • NRAS mutation • PIK3CA mutation • HER-2 mutation • KRAS G12D • PTEN mutation • KRAS G12V • MET exon 14 mutation • STK11 mutation • KRAS G12 • KRAS G13 • NRAS G12D • LAG3 expression • NRAS G13 • KRAS G13C
    |
    PD-L1 IHC 22C3 pharmDx • MI Tumor Seek™
    12ms
    Molecular characterization of nectin-4 in non-small cell lung cancer subtypes. (ASCO 2023)
    As enfortumab vedotin, an antibody-drug conjugate directed against nectin-4, has been FDA approved for advanced urothelial carcinoma, this holds treatment implications...NFE2L2 alterations in SQ and STK11, KEAP1 mutations in AD, which are associated with poor immunotherapy (IO) response, were enriched in Q4 tumors. This suggests that the immune landscape associated with high nectin-4 expression in NSCLC may be driven by the dysregulated KEAP1-NFE2L2 pathway. Targeted therapy towards nectin-4 may benefit these NSCLC subtypes that do not respond well to IO.
    PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • STK11 (Serine/threonine kinase 11) • CD8 (cluster of differentiation 8) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • IDO1 (Indoleamine 2,3-dioxygenase 1) • NECTIN4 (Nectin Cell Adhesion Molecule 4) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule)
    |
    PD-L1 expression • HER-2 mutation • STK11 mutation • KEAP1 mutation • NFE2L2 mutation • NECTIN4 expression
    |
    PD-L1 IHC 22C3 pharmDx • MI Tumor Seek™
    |
    Padcev (enfortumab vedotin-ejfv)
    12ms
    Molecular and immune analysis of adrenocortical carcinoma (ACC): Implications for immune checkpoint inhibition (ICI). (ASCO 2023)
    Querying a large real-world ACC patient dataset, we find somatic alterations and a low prevalence of ICI-related biomarkers (<10%), consistent with previous reports. Monocyte and endothelial cell infiltration in metastatic tumors suggests an immunosuppressive phenotype compared to primary tumors. Finally, identification of molecular alterations in tumors with distinct immune phenotypes may facilitate development of new therapeutic strategies in ACC.
    Checkpoint inhibition • Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • BRCA Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • TERT (Telomerase Reverse Transcriptase) • CDK4 (Cyclin-dependent kinase 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • ATRX (ATRX Chromatin Remodeler) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2)
    |
    PD-L1 expression • TP53 mutation • TMB-H • MSI-H/dMMR • ATRX mutation • CDK4 amplification • CTNNB1 mutation • HAVCR2 expression • TERT mutation • TERT promoter mutation • CDK4 mutation
    |
    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
    12ms
    Characterizing the role of PIM kinases in the prostate tumor immune microenvironment. (ASCO 2023)
    Our data suggest a strong association between PIM expression and increased MAPK activation score, T cell inflamed score, inflammatory, MHC class I and MHC class II gene expression, and differential immune cell infiltration. A better understanding of these differences will provide a rationale for tailored therapeutic approaches for PIM-expressing PC.
    KRAS (KRAS proto-oncogene GTPase) • AR (Androgen receptor) • IL6 (Interleukin 6) • B2M (Beta-2-microglobulin) • STAT3 (Signal Transducer And Activator Of Transcription 3) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • IL2 (Interleukin 2) • PIM1 (Pim-1 Proto-Oncogene) • HLA-B (Major Histocompatibility Complex, Class I, B) • TGFB1 (Transforming Growth Factor Beta 1) • HLA-DPA1 (Major Histocompatibility Complex, Class II, DP Alpha 1) • IL1B (Interleukin 1, beta) • TAP1 (Transporter 1) • HLA-C (Major Histocompatibility Complex, Class I, C) • KLK3 (Kallikrein-related peptidase 3) • PIM3 (Pim-3 Proto-Oncogene) • TNFSF13 (TNF Superfamily Member 13)
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    AR expression • MHC-II expression • PIM1 overexpression
    |
    MI Tumor Seek™
    12ms
    The molecular signature of gain-of-function (GOF) vs. non-GOF classification TP53 mutations in colorectal cancer. (ASCO 2023)
    In CRC, non-GOF mTP53 was prevalent in more than half of all cases. Compared to GOF mTP53, predictive biomarkers of response to immune checkpoint inhibitors (TMB and MSI-H/dMMR) were higher in this cohort albeit still relatively rare. Otherwise, differences in molecular signatures between GOF and non-GOF mTP53 did not contain clinically meaningful differences.
    Tumor mutational burden • MSi-H Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • BCL2L1 (BCL2-like 1) • BAX (BCL2-associated X protein) • CDC25C (Cell Division Cycle 25C) • CDK1 (Cyclin-dependent kinase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • BBC3 (BCL2 Binding Component 3) • GNRP (Ras-Specific Guanine Nucleotide-Releasing Factor 1)
    |
    TP53 mutation • KRAS mutation • TMB-H • MSI-H/dMMR • BRAF mutation • TP53 wild-type • MYC expression • TP53 R175H • BAX expression • TP53 R248Q • TP53 R273H • TP53 G245S • TP53 R196* • TP53 R213 • TP53 R273C
    |
    MI Tumor Seek™