^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    BIOMARKER:

    KMT2D mutation

    i
    Other names: KMT2D, Lysine Methyltransferase 2D, Histone-Lysine N-Methyltransferase 2D, Myeloid/Lymphoid Or Mixed-Lineage Leukemia 2, Lysine (K)-Specific Methyltransferase 2D, Trinucleotide Repeat Containing 21, Lysine N-Methyltransferase 2D, ALL1-Related Protein, MLL2, MLL4, ALR, Myeloid/Lymphoid Or Mixed-Lineage Leukemia Protein, Histone-Lysine N-Methyltransferase MLL2, Truncated Lysine Methyltransferase 2D, Kabuki Mental Retardation Syndrome, Kabuki Make-Up Syndrome, CAGL114, KABUK1, TNRC21, AAD10
    Entrez ID:
    8085
    Related biomarkers:
    Expression
    Mutation
    Others
    2d
    Altered TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR Predict Shorter Survival in Penile Squamous Cell Carcinoma. (PubMed, Mod Pathol)
    We detected 160 alterations with potential treatment implications, with 21.2% of samples showing alterations in the homologous recombination pathway. To the best of our knowledge, this study describes the largest cohort of pSCC with complex molecular-pathological, clinical, and prognostic analysis correlating with prognosis.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • KMT2D (Lysine Methyltransferase 2D) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • FAT1 (FAT atypical cadherin 1) • CHEK1 (Checkpoint kinase 1) • CASP8 (Caspase 8) • EPHA3 (EPH receptor A3) • GRIN2A (Glutamate Ionotropic Receptor NMDA Type Subunit 2A) • POT1 (Protection of telomeres 1) • EPHA7 (EPH Receptor A7)
    |
    PD-L1 expression • TP53 mutation • TMB-H • PIK3CA mutation • PD-L1 negative • TMB-L • KMT2D mutation • HRAS mutation • TP53 expression • CHEK1 mutation • GRIN2A mutation • CHEK1 expression
    5d
    Discover Mutational Differences Between Lung Adenocarcinoma and Lung Squamous Cell Carcinoma and Search for More Effective Biomarkers for Immunotherapy. (PubMed, Cancer Manag Res)
    We observed distinct mutation patterns and clinical factors between LUAD and LUSC, and noted that patients with TMB≥10 and PD-L1≥50% exhibited enhanced immunotherapy effects. Combining TMB≥10 and PD-L1≥50% proved to be a more effective predictor of immunotherapy efficacy.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • KMT2D (Lysine Methyltransferase 2D) • LRP1B (LDL Receptor Related Protein 1B) • KMT2C (Lysine Methyltransferase 2C) • FAT1 (FAT atypical cadherin 1) • RBM10 (RNA Binding Motif Protein 10)
    |
    PD-L1 expression • TP53 mutation • KMT2D mutation • MLL3 mutation
    9d
    Sustained yet non-curative response to lenalidomide in relapsed angioimmunoblastic T-cell lymphoma with acquired chidamide resistance: a case report with 10-year follow-up, genetic insights and literature review. (PubMed, Front Oncol)
    Notably, genes commonly mutated in AITL, including RHOA, TET2, DNMT3A, and IDH2, were absent in this case. A review of the literature highlights the heterogeneous genomic landscape of AITL and the diversity of treatment options available, underscoring the importance of tailored approaches to overcome resistance and improve outcomes in this distinct lymphoma subtype.
    Review • Journal
    |
    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • ARID1A (AT-rich interaction domain 1A) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • RHOA (Ras homolog family member A)
    |
    ARID1A mutation • TET2 mutation • KMT2D mutation • Chr del(5q)
    |
    lenalidomide • Epidaza (chidamide)
    17d
    Molecular characterization of ovarian squamous cell carcinoma originating from mature teratoma. (PubMed, J Mol Med (Berl))
    TP53 mutations found in 82% of ovarian SCC cases. CDKN2A mutations and 9p21.3 loss observed in 54.5% of ovarian SCC cohort.
    Journal
    |
    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • KMT2D (Lysine Methyltransferase 2D)
    |
    TP53 mutation • PIK3CA mutation • PTEN mutation • CDKN2A mutation • KMT2D mutation
    28d
    Mapping in silico genetic networks of the KMT2D tumour suppressor gene to uncover novel functional associations and cancer cell vulnerabilities. (PubMed, Genome Med)
    Our study thus illustrates how tumour suppressor gene LOF alterations can be exploited to reveal potentially targetable cancer cell vulnerabilities.
    Journal
    |
    KMT2D (Lysine Methyltransferase 2D) • WRN (WRN RecQ Like Helicase)
    |
    KMT2D mutation
    |
    HRO761
    1m
    The tissue and circulating cell-free DNA-derived genetic landscape of premalignant colorectal lesions and its application for early diagnosis of colorectal cancer. (PubMed, MedComm (2020))
    Through this endeavor, we identified two novel genes, CNTNAP5 and GATA6, implicated in CRC carcinogenesis. Overall, our findings reveal convincing biomarkers markers for detecting CRAs with a propensity for CRC development, highlighting the importance of early genetic screening in CRC prevention.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • GATA6 (GATA Binding Protein 6) • SOX9 (SRY-Box Transcription Factor 9)
    |
    TP53 mutation • PIK3CA mutation • KMT2D mutation
    3ms
    Next-generation integrated sequencing identifies poor prognostic factors in patients with MYD88-mutated chronic lymphocytic leukemia in Taiwan. (PubMed, Pathobiology)
    IGLL5, MYD88, and KMT2D mutations were enriched in Taiwanese CLL, and co-occurrence of MYD88 mutations with KMT2D or/and IGLL5 mutations was associated with a poorer prognosis.
    Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IGH (Immunoglobulin Heavy Locus) • KMT2D (Lysine Methyltransferase 2D) • IGLL5 (Immunoglobulin Lambda Like Polypeptide 5) • DSCAM (DS Cell Adhesion Molecule) • TCHH (Trichohyalin)
    |
    MYD88 mutation • KMT2D mutation • MYD88 L265P • IGLL5 mutation
    3ms
    Sintilimab combined with anlotinib and chemotherapy as second-line or later therapy in extensive-stage small cell lung cancer: a phase II clinical trial. (PubMed, Signal Transduct Target Ther)
    The trial design involved a combination therapy (sintilimab, anlotinib, and nab-paclitaxel) administered over six 21-day cycles, followed by maintenance sintilimab therapy. ctDNA analysis indicated that low on-treatment blood tumor mutation burden was associated with longer PFS and OS and a potential role of KMT2D mutation in treatment resistance. This combination therapy shows promising efficacy and a manageable safety profile as a second-line or later treatment for ES-SCLC, with genomic insights providing potential biomarkers for treatment response.
    P2 data • Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • KMT2D (Lysine Methyltransferase 2D)
    |
    KMT2D mutation
    |
    Focus V (anlotinib) • Tyvyt (sintilimab) • albumin-bound paclitaxel
    7ms
    Study of Modified Atkins Diet in Kabuki Syndrome (clinicaltrials.gov)
    P1, N=15, Active, not recruiting, Hugo W. Moser Research Institute at Kennedy Krieger, Inc. | Trial completion date: Dec 2024 --> Aug 2024
    Trial completion date
    |
    KMT2D (Lysine Methyltransferase 2D)
    |
    KMT2D mutation
    7ms
    LLS 2024 ELN-REFINED RISK STRATIFICATION IN OLDER ADULTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA TREATED WITH LOW-INTENSITY THERAPY (EHA 2024)
    Among patients ≥60 yrs with ND AML given LIT, the current 2022 ELN risk system classifies most (79%)patients as adverse risk and does not reliably distinguish favorable from intermediate-risk, highlighting thelimitations of the model in this patient population. We propose a refined LLS classification using a "mutationscore" incorporating IDH2, MLL2, KRAS and TP53 mutations for those previously assigned ELN 2022 adverserisk, as well as redefining the definition of LLS-favorable risk.
    Clinical
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • KMT2D (Lysine Methyltransferase 2D) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2)
    |
    TP53 mutation • KRAS mutation • FLT3-ITD mutation • IDH2 mutation • FLT3 mutation • KMT2D mutation • TP53 mutation + KRAS mutation • MLL2 mutation • KRAS mutation + TP53 mutation
    |
    FoundationOne® Heme CDx • LeukoStrat® CDx FLT3 Mutation Assay
    8ms
    Molecular pathogenesis of ameloblastoma. (PubMed, J Oral Pathol Med)
    The biological impact of these mutations in the pathogenesis of AM has yet to be elucidated. Further studies are needed to clarify the impact of these findings in the identification of novel biomarkers that could be useful for diagnosing, classifying, and molecular targeting this neoplasm.
    Review • Journal
    |
    BRAF (B-raf proto-oncogene) • KMT2D (Lysine Methyltransferase 2D)
    |
    BRAF V600E • BRAF V600 • KMT2D mutation
    8ms
    Case report: Mutation evolution in a patient with TdT positive high grade B cell lymphoma with MYC and BCL2 rearrangements following the treatment of concurrent follicular lymphoma and diffuse large B-cell lymphoma. (PubMed, Discov Oncol)
    This study reports a rare case of TdT positive "double hit" HGBL following the treatment of concurrent FL/DLBCL and highlights the mutation characteristics. Collectively, this study will help enrich the knowledge of TdT positive "double hit" HGBL transformed from FL/DLBCL.
    Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • FGFR3 (Fibroblast growth factor receptor 3) • CD20 (Membrane Spanning 4-Domains A1) • KMT2D (Lysine Methyltransferase 2D) • CHEK2 (Checkpoint kinase 2) • CREBBP (CREB binding protein) • BCL7A (BAF Chromatin Remodeling Complex Subunit BCL7A) • CCND3 (Cyclin D3) • MME (Membrane Metalloendopeptidase) • MUC4 (Mucin 4, Cell Surface Associated) • STAT6 (Signal transducer and activator of transcription 6) • ARID5B (AT-Rich Interaction Domain 5B) • DDX3X (DEAD-Box Helicase 3 X-Linked)
    |
    ATM mutation • MYC rearrangement + BCL2 rearrangement • KMT2D mutation • CHEK2 mutation • BCL2 expression • CD20 expression • MYC rearrangement • CD19 expression • BCL2 rearrangement • IGH translocation • BCL2 translocation
    8ms
    Integrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix. (PubMed, Proc Natl Acad Sci U S A)
    However, combinations of copanlisib/afatinib and copanlisib/elimusertib were significantly more effective in controlling NETc tumor growth. These findings define the genetic landscape of NETc and suggest that a large subset of these highly lethal malignancies might benefit from existing targeted therapies.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • MBD4 (Methyl-CpG Binding Domain 4, DNA Glycosylase) • PVT1 (Pvt1 Oncogene) • RPL10 (Ribosomal Protein L10)
    |
    KRAS mutation • PIK3CA mutation • ARID1A mutation • KMT2D mutation
    |
    Gilotrif (afatinib) • Aliqopa (copanlisib) • elimusertib (BAY 1895344)
    9ms
    Loss of CREBBP and KMT2D cooperate to accelerate lymphomagenesis and shape the lymphoma immune microenvironment. (PubMed, Nat Commun)
    Their combined deficiency preferentially impairs activation of immune synapse-responsive super-enhancers, pointing to a particular dependency for both co-activators at these specialized regulatory elements. Together, our data provide an example where chromatin modifier mutations cooperatively shape and induce an immune-evasive microenvironment to facilitate lymphomagenesis.
    Journal
    |
    CD8 (cluster of differentiation 8) • KMT2D (Lysine Methyltransferase 2D) • CREBBP (CREB binding protein)
    |
    KMT2D mutation
    9ms
    Urinary comprehensive genomic profiling assists in non-invasive detection and molecular staging of upper tract urothelial carcinoma (AUA 2024)
    uCGP can identify genomic features associated with UTUC and provide definitive results in cases of atypical cytology. Unique genomic patterns provide insight into tumor grade and origin. This study suggests uCGP can provide diagnostic and prognostic information for the evaluation for UTUC.
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ARID1A (AT-rich interaction domain 1A) • TERT (Telomerase Reverse Transcriptase) • KMT2D (Lysine Methyltransferase 2D) • CREBBP (CREB binding protein) • STAG2 (Stromal Antigen 2) • SOX4 (SRY-Box Transcription Factor 4)
    |
    PIK3CA mutation • HER-2 mutation • ARID1A mutation • KMT2D mutation • CREBBP mutation • ERBB3 mutation • STAG2 mutation • TERT mutation
    |
    UroAmp
    10ms
    Comprehensive genomic profiling to identify actionable alterations for breast cancer brain metastases in the Chinese population. (PubMed, ESMO Open)
    TMB and TILs were relatively low in BCBMs. Comparable consistency in actionable GAs was identified between BCBMs and matched PTs/ECMs. It was, therefore, logical to carry out genomic testing for BCBMs to identify potential new therapeutic targets when BCBM specimens were available, as ∼31% of samples carried additional actionable GAs.
    Journal • Tumor mutational burden • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • KMT2D (Lysine Methyltransferase 2D) • FGF3 (Fibroblast growth factor 3) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • RAD21 (RAD21 Cohesin Complex Component)
    |
    TP53 mutation • TMB-H • PIK3CA mutation • KMT2D mutation
    |
    FoundationOne® CDx
    10ms
    Genomic profiles and their relationships with clinical characteristics and immune features in cervical cancer. (PubMed, Transl Oncol)
    This study offers insights into the mutation characteristics of cervical cancer patients and identifies potential therapeutic.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    TMB (Tumor Mutational Burden) • NOTCH1 (Notch 1) • PD-1 (Programmed cell death 1) • KMT2D (Lysine Methyltransferase 2D) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • BARD1 (BRCA1 Associated RING Domain 1) • HLA-B (Major Histocompatibility Complex, Class I, B) • CEP290 (Centrosomal Protein 290) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
    |
    TMB-L • KMT2D mutation • HLA-A*03 • BARD1 mutation
    10ms
    Mutational patterns in therapy-related acute lymphoblastic leukemia subgroups: one step closer to unveiling the genetic odyssey. (PubMed, Leuk Lymphoma)
    Outcome was particularly poor in Ph + trALL compared to Ph+ de novo ALL, which seemed to be mitigated by allogeneic stem cell transplantation. Our findings further define trALL as a distinct entity but highlight the need for further molecular genome sequencing of somatic and germline variants to advance our understanding of trALL.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • KMT2A (Lysine Methyltransferase 2A) • KMT2D (Lysine Methyltransferase 2D)
    |
    TP53 mutation • KRAS mutation • DNMT3A mutation • KMT2A rearrangement • KMT2D mutation • MLL rearrangement
    11ms
    Follicular lymphoma presenting with symptomatic bone involvement: a clinicopathological and molecular analysis of 16 cases. (PubMed, Mod Pathol)
    All patients received rituximab +/- polychemotherapy as first-line treatment, and 7 local therapy (6 radiotherapy, 2 surgery)...FL may manifest as a localized or polyostotic bone disease. A minority represent PBL, while most reveal systemic disease.
    Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • BCL6 (B-cell CLL/lymphoma 6) • KMT2D (Lysine Methyltransferase 2D) • CD5 (CD5 Molecule) • TNFRSF14 (TNF Receptor Superfamily Member 14) • MME (Membrane Metalloendopeptidase)
    |
    KMT2D mutation • BCL6 rearrangement • BCL2 rearrangement
    |
    Rituxan (rituximab)
    11ms
    Feasibility of Circulating Tumor DNA Analysis in Patients with Follicular Lymphoma. (PubMed, Cancer Res Treat)
    Forty samples from patients receiving rituximab-containing immunochemotherapy were analyzed...Analysis of ctDNA mutations in plasma at diagnosis might help predict outcome of disease, while analysis during follow-up may help to monitor disease status of patients with advanced FL. However, the feasibility of ctDNA measurement must be improved in order for it to become an appropriate and clinically relevant test in FL patients.
    Journal • Tumor mutational burden • Circulating tumor DNA
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • CREBBP (CREB binding protein)
    |
    TP53 mutation • KMT2D mutation • CREBBP mutation • KMT2C mutation
    |
    Rituxan (rituximab)
    12ms
    Study of Modified Atkins Diet in Kabuki Syndrome (clinicaltrials.gov)
    P1, N=15, Active, not recruiting, Hugo W. Moser Research Institute at Kennedy Krieger, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    KMT2D (Lysine Methyltransferase 2D)
    |
    KMT2D mutation
    12ms
    Genetic and prognostic analysis of blastoid and pleomorphic mantle cell lymphoma: a multicenter analysis in China. (PubMed, Ann Hematol)
    First-line high-dose cytosine arabinoside exposure obtained survival benefits in these populations, and BTKi combination therapy as the front-line treatment had somewhat improvement in survival with no significant difference in the statistic...Patients with POD12 displayed a distinct mutation profile and a poor prognosis. New therapeutic drugs and clinical trials for B/P-MCL need to be further explored.
    Journal
    |
    TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • KMT2D (Lysine Methyltransferase 2D) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein) • FAT1 (FAT atypical cadherin 1) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
    |
    TP53 mutation • ATM mutation • CDKN2A mutation • KMT2D mutation
    |
    cytarabine
    12ms
    Somatic mutations of MLL4/COMPASS induce cytoplasmic localization providing molecular insight into cancer prognosis and treatment. (PubMed, Proc Natl Acad Sci U S A)
    Using a preclinical carcinogen model of bladder cancer in mouse, we demonstrate that truncated cytoplasmic MLL4 predicts response to targeted metabolic inhibition therapy for bladder cancer and could be developed as a biomarker for KMT2D-mutated cancers. We also highlight the broader potential for prognosis, patient stratification and treatment decision-making based on KMT2D mutation status in MLL4 truncation-relevant diseases, including human cancers and Kabuki Syndrome.
    Journal
    |
    KMT2D (Lysine Methyltransferase 2D)
    |
    KMT2D mutation • MLL mutation
    1year
    Recombinant Human Adenovirus Type 5 (H101) Intra-Tumor Therapy in Patients with Persistent, Recurrent, or Metastatic Cervical Cancer: Genomic Profiling Relating to Clinical Efficacy. (PubMed, Drug Des Devel Ther)
    We conducted an unprecedented work via a WES-based approach and provided preliminary insights into H101 treatment-induced genetic aberrations in which some genes (TTN, KMT2D, ALDOA, DNAH7, ADAP1, PTPN23, and THEMIS2) could be considered potential therapeutic targets of H101-containing treatment in cervical carcinoma. Moreover, the therapy-associated characteristics such as clonal evolution and a mutational signature may warrant further evaluation of H101 in clinical settings for treating cervical carcinoma.
    Journal • Tumor mutational burden • MSi-H Biomarker • Metastases
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • KMT2D (Lysine Methyltransferase 2D) • ALDOA (Aldolase Fructose-Bisphosphate A) • THEMIS2 (Thymocyte Selection Associated Family Member 2)
    |
    KMT2D mutation • TTN mutation • PTPN2 mutation
    |
    Oncorine (recombinant human adenovirus type 5)
    1year
    Exploring the molecular features and genetic prognostic factors of pulmonary high-grade neuroendocrine carcinomas. (PubMed, Hum Pathol)
    IHC for Rb was reliable for predicting LCNEC molecular subtypes, indicating its clinical value. NCOR2 and SPTA1 alterations were identified as prognostic factors that may provide therapeutic targets for patients with NEC.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • KMT2D (Lysine Methyltransferase 2D) • LRP1B (LDL Receptor Related Protein 1B) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • FAT3 (FAT Atypical Cadherin 3) • NCOR2 (Nuclear Receptor Corepressor 2) • SPTA1 (Spectrin Alpha) • AMPK (Protein Kinase AMP-Activated Catalytic Subunit Alpha 1) • SFTPA1 (Surfactant Protein A1)
    |
    TP53 mutation • EGFR mutation • NOTCH1 mutation • KMT2D mutation • HIF1A expression
    1year
    Gene mutation analysis of oral submucous fibrosis cancerization in Hainan Island. (PubMed, PeerJ)
    The mutation frequency of FLT4 gene was significantly higher than that of OSCC group (P < 0.05). FLT4 gene may be related to OSF cancerization and is expected to be an early diagnostic biomarker for OSF cancerization.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • KMT2A (Lysine Methyltransferase 2A) • MLH1 (MutL homolog 1) • KMT2D (Lysine Methyltransferase 2D) • FGFR4 (Fibroblast growth factor receptor 4) • MSH2 (MutS Homolog 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • APC (APC Regulator Of WNT Signaling Pathway) • FLT4 (Fms-related tyrosine kinase 4) • FLCN (Folliculin)
    |
    TP53 mutation • PIK3CA mutation • PTEN mutation • KMT2D mutation • APC mutation • MLH1 mutation
    1year
    Clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in Chinese population with mismatch repair deficient urothelial carcinoma: a real-world study. (PubMed, Front Immunol)
    Positive PD-L1 expression was found in 20% cases, but some patients positively responded to immunotherapy despite negative PD-L1 expression. Our findings provide valuable insights into the characteristics of dMMR UC in the Chinese population and highlights the relevance of genetic testing and immunotherapy biomarkers for treatment decisions.
    Journal • Real-world evidence • Mismatch repair • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Real-world
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C)
    |
    PD-L1 expression • TMB-H • MSI-H/dMMR • PD-L1 negative • KMT2D mutation
    1year
    Genetic Mutations in Primary Refractory Diffuse Large B-Cell Lymphoma: Next Generation Sequencing Analysis (ASH 2023)
    About 60-70% of DLBCL patients could be cured with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP), while the other patients show chemo-refractory or relapse of disease and have poor prognosis. ConclusionCIITA, RASSF54, STAT6, SYK were frequently mutated in primary refractory DLBCL in this study. Because of the small sample size, however, the prognostic significance of these mutations needed to be studied in further researches.
    Next-generation sequencing • IO biomarker
    |
    TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • KMT2D (Lysine Methyltransferase 2D) • SYK (Spleen tyrosine kinase) • PIM1 (Pim-1 Proto-Oncogene) • STAT6 (Signal transducer and activator of transcription 6) • PCLO (Piccolo Presynaptic Cytomatrix Protein)
    |
    KMT2D mutation
    |
    Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • vincristine
    1year
    Mutational Landscape of Diffuse Large B-Cell Lymphoma (DLBCL) in Mexican Patients (ASH 2023)
    Inclusion criteria: patients > 18 years, diagnosis of DLBCL, without previous treatment and candidate to be treated with RCHOP... This is the first approach to describe the genomic landscape in Latino-american population. The presence of EZH2 and KMT2 mutations were more frequent in female patients with mediastinal and bulky disease. After multivariate analysis, only the presence of EZH2 mutations was the only genomic factor influencing on OS.
    Clinical
    |
    TP53 (Tumor protein P53) • ARID1A (AT-rich interaction domain 1A) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • KMT2D (Lysine Methyltransferase 2D) • CREBBP (CREB binding protein)
    |
    TP53 mutation • MYD88 mutation • KMT2D mutation • EZH2 mutation
    |
    Rituxan (rituximab)
    1year
    Pucotenlimab in patients with advanced mismatch repair-deficient or microsatellite instability-high solid tumors: A multicenter phase 2 study. (PubMed, Cell Rep Med)
    Pucotenlimab is an effective treatment option for previously treated advanced dMMR/MSI-H solid tumors, and the predictive value of KMT2D mutation warrants further research. This study is registered with ClinicalTrials.gov: NCT03704246.
    P2 data • Journal • Mismatch repair • Microsatellite instability • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    MSI (Microsatellite instability) • KMT2D (Lysine Methyltransferase 2D)
    |
    MSI-H/dMMR • KMT2D mutation
    |
    Puyouheng (pucotenlimab)
    1year
    DNA damage response and repair gene mutations are associated with tumor mutational burden and outcomes to platinum-based chemotherapy/immunotherapy in advanced NSCLC patients. (PubMed, Diagn Pathol)
    DDR gene mutations are associated with tumor metastasis, TMB, and outcomes to platinum-based chemotherapy/immunotherapy in advanced NSCLC patients.
    Journal • Tumor mutational burden • IO biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • KMT2D (Lysine Methyltransferase 2D) • FANCG (FA Complementation Group G)
    |
    TP53 mutation • KRAS mutation • TMB-H • ALK mutation • KMT2D mutation • FANCG mutation
    1year
    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
    |
    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)
    |
    PD-L1 expression • EGFR mutation • MSI-H/dMMR • BRAF mutation • HER-2 negative • PIK3CA mutation • NTRK1 fusion • HER-2 expression • NF1 mutation • KMT2D mutation
    |
    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
    |
    Vitrakvi (larotrectinib)
    1year
    Emergence of Highly-Plastic B Cell States Cooperates with Early Immune Microenvironment Remodeling to Drive Follicular Lymphomagenesis (ASH 2023)
    In conclusion, our results provide a high-resolution view of events spanning FL progression and indicate a major role of early TME remodeling in establishing a suitable niche for progression. Early intervention aimed to target the B cell-tumor microenvironment interactions driving intra-tumoral heterogeneity may represent a promising therapeutic avenue against early disease and prevention of FL recurrence.
    IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • CD8 (cluster of differentiation 8) • KMT2D (Lysine Methyltransferase 2D) • CD4 (CD4 Molecule)
    |
    BCL2 overexpression • KMT2D mutation • BCL2 expression • BCL2 mutation
    1year
    Integrative Genomic and Transcriptomic Analysis Reveals Targetable Vulnerabilities in Angioimmunoblastic T-Cell Lymphoma (ASH 2023)
    Low mRNA expression of PHLPP2 predicted poor prognosis (p=.03) and engineered PHLPP2 loss showed enhanced PI(3)K activation and FOXO1 inactivation in CD4+ T-cells in-vitro. Thus, we defined the genomic landscape for AITL, which is largely characterized by epigenetic alterations, TCR signaling and PI3K/AKT dysregulation, which may be amenable for therapeutic targeting.
    IO biomarker • Omic analysis
    |
    PTEN (Phosphatase and tensin homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CD20 (Membrane Spanning 4-Domains A1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CD163 (CD163 Molecule) • CD4 (CD4 Molecule) • JAK3 (Janus Kinase 3) • RHOA (Ras homolog family member A) • CD68 (CD68 Molecule) • PHLPP1 (PH Domain And Leucine Rich Repeat Protein Phosphatase 1) • SOCS1 (Suppressor Of Cytokine Signaling 1) • STAT1 (Signal Transducer And Activator Of Transcription 1) • VAV1 (Vav Guanine Nucleotide Exchange Factor 1) • HLPP2 (PH Domain And Leucine Rich Repeat Protein Phosphatase 2) • PHLPP2 (PH Domain And Leucine Rich Repeat Protein Phosphatase 2)
    |
    IDH2 mutation • DNMT3A mutation • TET2 mutation • KMT2D mutation • JAK3 mutation • IDH2 R172 • RHOA G17V
    1year
    Phase II Trial of Ibrutinib in Previously Untreated High-Risk Smoldering Mantle Cell Lymphoma (ASH 2023)
    Ibrutinib demonstrated significant efficacy with manageable toxicities in previously untreated patients with high-risk smoldering MCL.
    P2 data
    |
    TP53 (Tumor protein P53) • KMT2D (Lysine Methyltransferase 2D) • BIRC3 (Baculoviral IAP repeat containing 3)
    |
    TP53 mutation • TP53 wild-type • KMT2D mutation • MYC positive
    |
    Imbruvica (ibrutinib)
    1year
    A Multi-Omic Study Unveils a Clonal Population of TET2-Mutated Infiltrating T-Cells in Germinal Center B Cell Lymphomas (DLBCL and FL) (ASH 2023)
    Moreover, our findings support the critical role of the tumor microenvironment for the persistence and development of the tumor clone. The finding of a TET2 mutated clone in the infiltrating T cells of all the patients is particularly noteworthy, as it may suggest the possible presence of clonal lymphopoiesis.
    Clinical • PD(L)-1 Biomarker • IO biomarker
    |
    ATM (ATM serine/threonine kinase) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • LAG3 (Lymphocyte Activating 3) • B2M (Beta-2-microglobulin) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • NOTCH2 (Notch 2) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CD4 (CD4 Molecule) • CD5 (CD5 Molecule) • GNA13 (G Protein Subunit Alpha 13) • RHOA (Ras homolog family member A) • MME (Membrane Metalloendopeptidase)
    |
    TET2 mutation • KMT2D mutation • EZH2 mutation • CD8 expression • LAG3 expression • CD4 expression
    1year
    Mutations in Histone Lysine Methyltransferase Genes Are Associated with Autoimmune Cytopenias (ASH 2023)
    Conclusion We report for the first time that patients with autoimmune cytopenias have a high frequency of variants in MT genes. Median allelic frequency close to 50% suggests potential germline predisposition to immune dysregulation and autoimmunity however further studies are needed to better understand the impact of these observations.
    Epigenetic controller
    |
    KMT2A (Lysine Methyltransferase 2A) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • KDM6A (Lysine Demethylase 6A)
    |
    KMT2D mutation • KMT2C mutation • KDM6A mutation • MLL3 mutation
    1year
    CD58 Genetic Alterations and Its Contribution to Upregulation of PD-L1 and IDO Via LYN/CD22/SHP1 Axis in DLBCL (ASH 2023)
    Patients with CD58 mutation, copy number loss or low expression exhibited lower complete response rates following first-line R-CHOP therapy, as well as significantly poorer PFS and OS... Our study comprehensively characterized CD58 genetic alterations in DLBCL. We demonstrated that CD58 downregulation or mutation led to upregulation of PD-L1 and IDO expression mainly by regulating the LYN/CD22/SHP1 axis. Moreover, we explored strategies to directly activate CD2 co-stimulatory signaling or in combination with immune checkpoint inhibitors to address the diverse effects of CD58 alterations.
    PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • JAK2 (Janus kinase 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD8 (cluster of differentiation 8) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • CD22 (CD22 Molecule) • CD4 (CD4 Molecule) • LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase) • CD58 (CD58 Molecule) • CD2 (CD2 Molecule)
    |
    PD-L1 expression • MYD88 mutation • KMT2D mutation • CD79B mutation • IDO1 expression • CD58 mutation
    |
    Rituxan (rituximab)
    1year
    Longitudinal Noninvasive Surveillance & Fragmentomic Characterization of Follicular Lymphoma (ASH 2023)
    Depth of response was similar between rituximab monotherapy and cytotoxic regimens, with median -2.2 log10 fold change from baseline...Frequent detectable MRD in radiographic remission suggests that integrating molecular surveillance may augment serial imaging in the long-term management of FL. Simultaneous inferred gene expression from FL cfDNA appears to hold promise, including for noninvasive detection of transformation.
    IO biomarker
    |
    TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • KMT2D (Lysine Methyltransferase 2D) • CREBBP (CREB binding protein)
    |
    TP53 mutation • KMT2D mutation • CREBBP mutation
    |
    Rituxan (rituximab)