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

MLL3 mutation

i
Other names: MLL3, KMT2C, Lysine Methyltransferase 2C, Histone-Lysine N-Methyltransferase 2C, Myeloid/Lymphoid Or Mixed-Lineage Leukemia Protein 3, Lysine (K)-Specific Methyltransferase 2C, Histone-Lysine N-Methyltransferase, H3 Lysine-4 Specific, Myeloid/Lymphoid Or Mixed-Lineage Leukemia 3, Histone-Lysine N-Methyltransferase MLL3, Lysine N-Methyltransferase 2C, ALR-Like Protein, KLEFS2
Entrez ID:
Related biomarkers:
Associations
2ms
MYC-rearranged mature B-cell lymphomas in children and young adults are molecularly Burkitt Lymphoma. (PubMed, Blood Cancer J)
TP53 and KMT2C mutations conferred inferior outcome (3-year EFS P < 0.05). Overall, MYC-R lymphomas in CAYA have a molecular profile similar to BL regardless of their high-grade or DLBCL morphology, whereas MYC-non-R has more heterogeneous genetic alterations closer to that of DLBCL.
Journal • IO biomarker
|
TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • KMT2C (Lysine Methyltransferase 2C)
|
TP53 mutation • MYC expression • KMT2C mutation • MYC rearrangement • BCL6 translocation • MLL3 mutation
7ms
KMT2C mutation as a predictor of immunotherapeutic efficacy in colorectal cancer. (PubMed, Sci Rep)
Meanwhile, KMT2C mutation was associated with higher tumor mutation burden, MSI score, higher levels of immune-associated T cells, neutrophil, and M1-type macrophages. Our study suggested that KMT2C mutation might be a potential positive predictor for CRC immunotherapy.
Journal • Tumor mutational burden • IO biomarker
|
TMB (Tumor Mutational Burden) • KMT2C (Lysine Methyltransferase 2C)
|
KMT2C mutation • MLL3 mutation
8ms
A comprehensive histomolecular characterization of meningioangiomatosis: Further evidence for a precursor neoplastic lesion. (PubMed, Brain Pathol)
The DNA-methylation profile, using a t-distributed stochastic neighbor embedding analysis, evidenced that MAM (pure or associated with meningiomas) clustered in a separate group from pediatric meningiomas. The present results seem to suggest that MAM represents a neoplastic lesion and encourage the further study of similar additional series so that it may be included in a future WHO classification.
Journal
|
KMT2C (Lysine Methyltransferase 2C) • NF2 (Neurofibromin 2)
|
KMT2C mutation • MLL3 mutation
8ms
Unraveling trajectories from aplastic anemia to hematologic malignancies: genetic and molecular insights. (PubMed, Front Oncol)
Monosomy 7's prevalence and the occurrence of PTPN11 mutations suggest predictive and prognostic significance. Clonal evolution underscores the complexity of disease progression.
Journal
|
PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • KMT2C (Lysine Methyltransferase 2C)
|
PTPN11 mutation • KMT2C mutation • MLL3 mutation
10ms
Germline variants in early and late-onset Brazilian prostate cancer patients. (PubMed, Urol Oncol)
Our findings contribute to a deeper understanding of the genetic factors associated with PCa susceptibility in different age groups, especially among the Brazilian population. This is the first investigation to explore germline variants specifically in younger Brazilian PCa patients, with high relevance given the genetic diversity of the population in Brazil. Additionally, our work presents evidence of functionally deleterious germline variants within the KMT2C gene among Brazilian PCa patients. The identification of novel and functionally significant variants in the KMT2C gene emphasizes its potential role in PCa development and warrants further investigation.
Journal • BRCA Biomarker
|
BRCA2 (Breast cancer 2, early onset) • KMT2C (Lysine Methyltransferase 2C)
|
KMT2C mutation • MLL3 mutation
12ms
Comprehensive genomic profiling reveals prognostic signatures and insights into the molecular landscape of colorectal cancer. (PubMed, Front Oncol)
Noteworthy BRAF and ARID2 protein expression decreases detected in patients with their respective mutations. The integration of our analyses furnishes crucial insights into CRC's molecular characteristics, drug responsiveness, and the construction of a four-gene mutation signature for predicting CRC prognosis.
Journal
|
BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • GNAQ (G Protein Subunit Alpha Q) • KMT2C (Lysine Methyltransferase 2C) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein) • FAT1 (FAT atypical cadherin 1) • ARID2 (AT-Rich Interaction Domain 2) • TGFB1 (Transforming Growth Factor Beta 1) • PI3K (Phosphoinositide 3-kinases)
|
BRAF mutation • GNAQ mutation • AR mutation • KMT2C mutation • MLL3 mutation
12ms
Predictive biomarkers of response and survival following immunotherapy with a PD-L1 inhibitor benmelstobart (TQB2450) and antiangiogenic therapy with a VEGFR inhibitor anlotinib for pretreated advanced triple negative breast cancer. (PubMed, Signal Transduct Target Ther)
Patients with both low MSAF and low bTMB showed a notably better objective response to anlotinib plus TQB2450 (70% vs. 11%, P < 0.001) and a significantly longer median PFS (11.0 vs. 2.9 months, P < 0.001) than patients with other scenarios. Our findings support future studes and validation of MSAF and the combined bTMB-MSAF classification as predictive biomarkers of immune checkpoint inhibitor-based regimens in advanced TNBC patients.
Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases
|
PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • KMT2C (Lysine Methyltransferase 2C)
|
TP53 mutation • TMB-H • PIK3CA mutation • MLL mutation • MLL3 mutation
|
Focus V (anlotinib) • benmelstobart (APL-502)
1year
Intestinal-Type Adenocarcinoma in Head and Neck: Dissecting Oncogenic Gene Alterations Through Whole Transcriptome and Exome Analysis. (PubMed, Mod Pathol)
This changed the activity of multiple genes/gene clusters, supporting oncogenicity mostly via pathways of signaling, dedifferentiation, proliferation, migration, immune and inflammatory deregulation, indicating a truly epigenetic event as the root cause for the heterogeneous diversity of these enteric types of cancer. The data of this study form the basis for understanding cell fate determination and cellular homeostasis in the normal respiratory mucosa at different anatomic sites and show the contribution of different mucosal components to the etiology/molecular pathology of ITAC.
Journal
|
KMT2C (Lysine Methyltransferase 2C)
|
KMT2C mutation • MLL mutation • MLL3 mutation
1year
Transcriptomic Analysis of Clonal Hematopoiesis in Solid Tumors Reveals Driver Mutation-Specific Patterns of Immune Dysregulation (ASH 2023)
This work demonstrates that while general inflammatory changes are evident at the tumor level with CH, there is a critical need to recognize the nuances of CH-associated immune mechanisms in cancer, which appear to vary by cancer type and CH driver. Ongoing efforts will continue to characterize the TIME of the other TCGA cancers through transcriptomic analysis and in situ histological imaging. This study also provides some early clinical evidence for the selection of KMT2C variants in cancer patients, though more work is needed to understand their clonal dynamics and clinical implications.
IO biomarker • Omic analysis
|
DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2C (Lysine Methyltransferase 2C) • CHI3L1 (Chitinase 3-like 1) • CXCL6 (C-X-C Motif Chemokine Ligand 6) • KLRC2 (Killer Cell Lectin Like Receptor C2)
|
DNMT3A mutation • ASXL1 mutation • KMT2C mutation • MLL3 mutation
1year
Whole Genome and Transcriptome Sequencing of 21 Paired Chronic and Blast Phase CML Cases: Acquisition of Genomic Alterations, Changes in the Transcriptomic Profiles and Occurrence of B-Cell Receptor Rearrangements (ASH 2023)
1) Extensive genetic profiling indicated a substantial clonal evolution in the progression from CP to BP CML including loss of ASXL1 mutations, expansion of RUNX1 mutated clones, multiple CNA, and the frequent acquisition of a BCR rearrangement in BP with a transcriptomic phenotype resembling B-ALL. 2) A subset of CML cases in CP already showed a transcriptomic phenotype resembling acute leukemia indicating a rapid progression to BP. 3) The presence of a RUNX1 mutated subclone or a clonal BCR rearrangement seem to represent a warning signal in CML CP.
Clinical
|
ABL1 (ABL proto-oncogene 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • WT1 (WT1 Transcription Factor) • BCOR (BCL6 Corepressor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • MECOM (MDS1 And EVI1 Complex Locus) • MGA (MAX Dimerization Protein MGA) • MLLT3 (MLLT3 Super Elongation Complex Subunit)
|
DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • CDKN2A deletion • TET2 mutation • MLL rearrangement • BCOR mutation • IKZF1 deletion • WT1 mutation • MECOM rearrangement • SETD2 mutation • ABL1 fusion • MGA mutation • MLL3 mutation
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
Management of Hyperleukocytosis in Pediatric Acute Myeloid Leukemia Using Immediate Chemotherapy without Leukapheresis, in Protocol NOPHO-DBH AML-2012 (ASH 2023)
Protocol guidelines recommended immediate start of the first chemotherapy course (starting with etoposide [ETO] monotherapy for 5 days at 150 mg/m2 once daily) followed randomized by either cytarabine/mitoxantrone (MEC) or cytarabine/daunoxome or daunorubicin (D[x]EC). The NOPHO-DBH AML 2012 protocol is very effective in pediatric AML. The first chemotherapy course starts with five consecutive days of ETO monotherapy. We made use of this "ETO-window" in the management of HL patients, omitting invasive methods to reduce high WBCs.
Clinical
|
FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • MLLT3 (MLLT3 Super Elongation Complex Subunit)
|
FLT3-ITD mutation • NPM1 mutation • KMT2A rearrangement • MLL rearrangement • RUNX1-RUNX1T1 fusion • MLL3 mutation
|
cytarabine • etoposide IV • daunorubicin • mitoxantrone
1year
Genomic Characterization of Acute Myeloid Leukemia with Aberrations of Chromosome 7: A Multinational Cohort of 523 Patients (ASH 2023)
Our results offer novel insights into the genomic landscape and clonal trajectory of AML with abn(7). This work unravels formerly underestimated genetic lesions (KMT2Cmut) and alterations with high prognostic impact (abnTP53 and IDH2mut) for better future risk stratification.
Clinical
|
KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • NF1 (Neurofibromin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • ETV6 (ETS Variant Transcription Factor 6) • KMT2C (Lysine Methyltransferase 2C) • FAT1 (FAT atypical cadherin 1) • CUX1 (cut like homeobox 1) • TACC2 (Transforming Acidic Coiled-Coil Containing Protein 2)
|
TP53 mutation • KRAS mutation • BRAF mutation • FLT3 mutation • TP53 wild-type • KMT2C mutation • Chr del(7q) • MLL3 mutation
1year
KMT2C expression and DNA homologous recombination repair factors in lung cancers with a high-grade fetal adenocarcinoma component. (PubMed, Transl Lung Cancer Res)
These results support the hypothesis that loss of KMT2C function decreases the expression of the HRR factors in H-FLACs. H-FLACs with low KMT2C expression may be a good indication for poly (ADP-ribose) polymerase (PARP) inhibitor-based therapy.
Journal • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • KMT2C (Lysine Methyltransferase 2C) • ATR (Ataxia telangiectasia and Rad3-related protein)
|
KMT2C mutation • BRCA1 expression • ATM expression • BRCA2 expression • MLL3 mutation
1year
Differential DNA Mutation Profiles in Multiple Myeloma Patients: Implications of PET/CT Findings (IMW 2023)
We found that mutation distribution varied according to PET/CT results, with patients exhibiting FL > 3 showing a higher frequency of PABPC1 and KMT2C mutations. Further studies are warranted to gain a better understanding of the genetic background associated with positive PET/CT findings in MM.
Clinical
|
TP53 (Tumor protein P53) • ATM (ATM serine/threonine kinase) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2C (Lysine Methyltransferase 2C) • EP300 (E1A binding protein p300) • NCOR1 (Nuclear Receptor Corepressor 1) • HUWE1 (HECT UBA And WWE Domain Containing E3 Ubiquitin Protein Ligase 1) • ACTG1 (Actin Gamma 1) • PABPC1 (Poly(A) Binding Protein Cytoplasmic 1)
|
KMT2C mutation • MLL3 mutation
1year
Follicular Dendritic Cell Sarcoma With Associated Novel FBXW7 and KMT2C Mutations Identified by Targeted Genome Sequencing (CAP 2023)
KMT2C A2254T has only been reported in astrocytoma. To our knowledge, this is the first case report of FBXW7 and KMT2C mutations in FDCS, which may indicate biologic and therapeutic relevance (Figure 1.82, A–D).
FBXW7 (F-Box And WD Repeat Domain Containing 7) • KMT2C (Lysine Methyltransferase 2C) • BIRC3 (Baculoviral IAP repeat containing 3) • CR1 (Complement C3b/C4b Receptor 1) • FCER2 (Fc Fragment Of IgE Receptor II)
|
KMT2C mutation • MTOR mutation • KIT V559 • MLL3 mutation
|
FoundationOne® Heme CDx
over1year
Expanding the spectrum of eosinophilic solid and cystic renal cell carcinoma: molecular characterisation of borderline neoplasms from 25 patients reveals frequent alterations of TSC1, TSC2, and MTOR (ECP 2023)
However, keratin 20 positivity can also be found in occasional non-ESC tumors. The morphologic spectrum of ESC is probably broader than previously thought, as only 3 of the most convincing 11 ESC tumors were originally diagnosed as such.
Clinical
|
PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • mTOR (Mechanistic target of rapamycin kinase) • KMT2C (Lysine Methyltransferase 2C) • TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1) • KRT20 (Keratin 20)
|
PIK3CA mutation • KMT2C mutation • MLL3 mutation
over1year
Comprehensive genomic profiling of penile squamous cell carcinoma and the impact of human papillomavirus status on immune-checkpoint inhibitor-related biomarkers. (PubMed, Cancer)
Penile squamous cell carcinoma (pSCC) is a rare and aggressive malignancy in the advanced setting, with poor prognosis and little success with immune-checkpoint inhibitors (ICIs) in an unselected patient approach. Human papillomavirus (HPV) infection is a known risk factor for pSCC; its impact on genomic tumor profiling is less defined. Using next-generation sequencing, we explored the genetic landscape and ICI-related biomarkers of pSCC and HPV-driven oncogenic molecular signatures. Our results indicate that HPV-positive and HPV-negative pSCCs are molecularly distinct tumors. Increased tumor mutational burden is associated with HPV-positive tumors, and could serve as a biomarker for predicting therapeutic response to ICI-based therapies. Our results support the growing literature indicating that HPV status in pSCC can be used to guide patient stratification in ICI-based clinical trials.
Checkpoint inhibition • Journal • Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • KMT2C (Lysine Methyltransferase 2C) • FGF3 (Fibroblast growth factor 3)
|
PD-L1 expression • TMB-H • MSI-H/dMMR • PIK3CA mutation • CDKN2A mutation • KMT2C mutation • FGF3 amplification • MLL3 mutation
|
VENTANA PD-L1 (SP142) Assay
over1year
The epigenetic modifier lysine methyltransferase 2C is frequently mutated in gastric remnant carcinoma. (PubMed, J Pathol Clin Res)
In addition, KMT2C mutations were positively correlated with favorable outcomes in immune checkpoint inhibitor-treated pan-cancer patients and associated with higher intratumoral CD3 , CD8 tumor-infiltrating lymphocyte counts, and PD-L1 expression in GRC samples (p = 0.018, 0.092, 0.047, 0.010, and 0.034, respectively). Our dataset provides a platform for information and knowledge mining of the genomic characteristics of GRC and helps to frame new therapeutic approaches for this disease.
Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • ARID1A (AT-rich interaction domain 1A) • CD8 (cluster of differentiation 8) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1)
|
PD-L1 expression • ARID1A mutation • KMT2D mutation • KMT2C mutation • MLL3 mutation
over1year
Implications of KMT2C knockdown for DNA damage repair in breast cancer (ESMO 2023)
Conclusions KMT2C loss-of-function in breast cancer may impact DNA damage response pathways including homologous recombination and therefore be implicated in response to established treatments such as PARP-inhibitors. Further study including mapping of co-dependencies by whole genome siRNA screens in KMT2C-mutant breast cancer cells to identify synthetic lethality targets, as well as cell toxicity assays, are being performed in light of these results.
BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • KMT2C (Lysine Methyltransferase 2C) • RAD51 (RAD51 Homolog A) • RAD54L (DNA Repair And Recombination Protein RAD54) • POLD3 (DNA Polymerase Delta 3)
|
KMT2C mutation • MLL3 mutation
over1year
Mutations in epigenetic regulator KMT2C detected by liquid biopsy are associated with worse survival in prostate cancer patients. (PubMed, Oncol Res)
Lastly, we investigated the predictive value of KMT2C mutations in individuals receiving conventional combined anti-androgen blockade (CAB) and abiraterone (ABI) as measured by PSA progression-free survival (PSA-PFS)...KMT2C-mutated patients showed worse survival compared to KMT2C-WT patients in terms of both CRFS and OS, and KMT2C mutations were associated with STK11 and CTNNB1 mutations. Furthermore, KMT2C mutations indicated rapid progression during CAB therapy and could serve as a potential biomarker to predict therapeutic response in prostate cancer.
Journal • Liquid biopsy • Biopsy
|
STK11 (Serine/threonine kinase 11) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • KMT2C (Lysine Methyltransferase 2C) • CDK7 (Cyclin Dependent Kinase 7)
|
STK11 mutation • CTNNB1 mutation • KMT2C mutation • MLL3 mutation
|
abiraterone acetate
over1year
Therapeutic targeting of metabolic vulnerabilities in cancers with MLL3/4-COMPASS epigenetic regulator mutations. (PubMed, J Clin Invest)
Finally, we demonstrated that tumors with MLL3 and/or MLL4 mutations were highly sensitive to lometrexol in vivo, both in culture and in animal models of cancer. Our results depicted a targetable metabolic dependency arising from epigenetic factor deficiency, providing molecular insight to inform therapy for cancers with epigenetic alterations secondary to MLL3/4 COMPASS dysfunction.
Journal
|
KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C)
|
KMT2D mutation • MLL3 mutation
|
lometrexol (T-64)
over1year
Molecular profiling of a real-world breast cancer cohort with genetically inferred ancestries reveals actionable tumor biology differences between European ancestry and African ancestry patient populations. (PubMed, Breast Cancer Res)
We observed significant differences in mutational spectra, gene expression, and relevant transcriptional signatures between patients with genetically determined African and European ancestries, particularly within the HR+/HER2- BC and TNBC subtypes. These findings could guide future development of treatment strategies by providing opportunities for biomarker-informed research and, ultimately, clinical decisions for precision oncology care in diverse populations.
Journal • Real-world evidence • Real-world
|
HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • KMT2C (Lysine Methyltransferase 2C) • ATRX (ATRX Chromatin Remodeler) • HSPA1A (Heat Shock Protein Family A (Hsp70) Member 1A) • RPL10 (Ribosomal Protein L10)
|
HER-2 negative • PIK3CA mutation • KMT2C mutation • MLL3 mutation
over1year
Genomic characterization of MSI-H and TMB in gastrointestinal cancer. (ASCO 2023)
This study demonstrated that MSI-H is highly correlated with TMB-H, providing a new insight of evaluating gastrointestinal cancer treatment on MSI-H patients. The study also revealed novel MSI-H genetic mutation landscape for KMT gene family. Concurrent with recent researches, this study further boosts the potential of KMT genes to be used as a biomarker in both diagnosis and immunotherapy treatment.
Tumor mutational burden • MSi-H Biomarker • IO biomarker
|
TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • KMT2B (Lysine Methyltransferase 2B)
|
TMB-H • MSI-H/dMMR • MLL3 mutation
over1year
Journal
|
KMT2A (Lysine Methyltransferase 2A) • MLLT3 (MLLT3 Super Elongation Complex Subunit)
|
KMT2A mutation • MLL3 mutation
over1year
Epigenetic regulator KMT2C mutation detected by liquid biopsy is associated with worse survival in prostate cancer patients (AUA 2023)
KMT2C -mutated patients showed worse survival compared to KMT2C -WT patients in terms of both CFS and OS, and KMT2C mutation was associated with STK11 and CTNNB1 mutations. Furthermore, KMT2C mutation was significantly associated with survival in certain patient subgroups, such as patients with PI3K and WNT pathway mutation, etc.
Clinical • Liquid biopsy • Biopsy
|
STK11 (Serine/threonine kinase 11) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • KMT2C (Lysine Methyltransferase 2C) • CDK7 (Cyclin Dependent Kinase 7)
|
STK11 mutation • CTNNB1 mutation • KMT2C mutation • MLL3 mutation
over1year
Loss of Kmt2c in vivo leads to EMT, mitochondrial dysfunction and improved response to lapatinib in breast cancer. (PubMed, Cell Mol Life Sci)
Publicly available clinical datasets revealed an association of low Kmt2c gene expression and better long-term outcome. Collectively, our findings solidify the role of KMT2C as a tumour suppressor in breast cancer and identify dependencies that could be therapeutically amenable.
Preclinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • KMT2C (Lysine Methyltransferase 2C)
|
MLL3 mutation
|
lapatinib
almost2years
Frequently mutated genes in predicting the relapse of stage I lung adenocarcinoma. (PubMed, Clin Transl Oncol)
Three hundred and twenty-nine non-synonymous somatic variants were identified in 161 genes among these 35 patients. EGFR, TP53, LRP1B, RBM10, KRAS, NTRK3, RB1, ALK, APC, FAT2, KEAP1, MED12 and MLL3 were described as frequently mutated genes with prevalence more than 10%. Patients harboring KRAS mutation had more relapse in 1 year after surgical resection. For the expression of these frequently mutated genes in 149 stage I patients, multivariate Cox regression analyses showed that the expression of RBM10 was positively associated with RFS in all patients (HR 0.40, 95% CI 0.15-1.0, p = 0.052), and the expression of APC was negative associated with RFS in patients with EGFR mutations (HR 3.10, 95% CI 1.54-6.26, p = 0.002). Stage I LUAD patients with KRAS mutation or low RBM10 expression are inclined to receive more positive intervention rather than just disease surveillance.
Journal
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • RB1 (RB Transcriptional Corepressor 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • LRP1B (LDL Receptor Related Protein 1B) • KMT2C (Lysine Methyltransferase 2C) • RBM10 (RNA Binding Motif Protein 10) • FAT2 (FAT Atypical Cadherin 2)
|
KRAS mutation • EGFR mutation • KEAP1 mutation • RBM10 mutation • MLL3 mutation
almost2years
Role of epigenetic regulator KMT2C mutation detected by liquid biopsy in survival in patients with prostate cancer. (ASCO-GU 2023)
KMT2C-mutated patients showed worse survival compared to KMT2C-WT patients in terms of both CFS and OS, and KMT2C mutation was associated with STK11 and CTNNB1 mutations. Furthermore, KMT2C mutation was significantly associated with survival in certain patient subgroups, such as patients with PI3K and WNT pathway mutation, etc.
Clinical • Liquid biopsy • Biopsy
|
STK11 (Serine/threonine kinase 11) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • KMT2C (Lysine Methyltransferase 2C) • CDK7 (Cyclin Dependent Kinase 7)
|
STK11 mutation • CTNNB1 mutation • KMT2C mutation • MLL3 mutation
almost2years
MLL3 loss drives metastasis by promoting a hybrid epithelial-mesenchymal transition state. (PubMed, Nat Cell Biol)
Furthermore, BET inhibition effectively suppressed the growth of MLL3-mutant primary tumours and metastases. These results uncovered MLL3 mutation as a key driver of hybrid EMT and metastasis in breast cancer that could be targeted therapeutically.
Journal
|
IFNG (Interferon, gamma) • KMT2C (Lysine Methyltransferase 2C)
|
KMT2C mutation • MLL3 mutation
almost2years
Lineage switch in a pediatric patient with KMT2A-MLLT3 from acute megakaryoblastic leukemia to T cell acute lymphoblastic leukemia at the fourth relapse after allo-HSCT: with literature review. (PubMed, Int J Hematol)
She also developed a somatic mutation (c.7177C > T p.Q2393X) of NOTCH1 at the fourth relapse. This sequential phenotypic and cytogenetic study may yield valuable insights into the mechanism of AMKL to T-ALL lineage switch and possible implications for treatment selection.
Review • Journal
|
NOTCH1 (Notch 1) • KMT2A (Lysine Methyltransferase 2A) • MLLT3 (MLLT3 Super Elongation Complex Subunit)
|
MLL3 mutation
almost2years
Integrated genomic analyses of hepatocellular carcinoma. (PubMed, Hepatol Int)
Unique genomic alterations were observed in our Taiwanese HCC patients. Molecular classification using apoptosis-related genes could lead to new therapeutic approaches for HCC.
Journal
|
TP53 (Tumor protein P53) • ARID1A (AT-rich interaction domain 1A) • CD8 (cluster of differentiation 8) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • KMT2C (Lysine Methyltransferase 2C) • CD4 (CD4 Molecule) • ALDH2 (Aldehyde Dehydrogenase 2 Family Member)
|
KMT2C mutation • MLL3 mutation
almost2years
From Generic RNA-Based MRD Assessment Towards Patient-Specific Genomic (DNA-based) MRD in AML and Other Non-B Cell Acute Leukemia (ASH 2022)
MRD was quantified by using a standard curve derived from serial dilutions from the diagnostic DNA. Quantitative range, sensitivity and background were determined according to the ESG-MRD-ALL guidelines.
Clinical
|
ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • FGFR1 (Fibroblast growth factor receptor 1) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ETV6 (ETS Variant Transcription Factor 6) • AFF1 (AF4/FMR2 Family Member 1) • RANBP2 (RAN Binding Protein 2) • NUP214 (Nucleoporin 214) • CBFA2T3 (CBFA2/RUNX1 Partner Transcriptional Co-Repressor 3) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • DEK (DEK Proto-Oncogene) • AFDN (Afadin, Adherens Junction Formation Factor)
|
NPM1 mutation • TP53 deletion • MLL3 mutation
2years
Recurrent KMT2C Mutations As Clonal Hematopoiesis Is Common after Chemotherapy Exposure in Hodgkin's Lymphoma Patients (ASH 2022)
Peripheral mononuclear cell samples obtained from 19 HL patients treated at our center with ICI (14 nivolumab only, 1 pembrolizumab only, and 4 both) were sequenced. Prior studies have demonstrated that KMT2C deletions enhance hematopoietic stem cell self-renewal and do give a fitness advantage in the presence of chemotherapy. None of the patients in our cohort has developed therapy-related MDS/AML though it could be a risk in the future.
Clinical • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
|
DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2C (Lysine Methyltransferase 2C) • NOTCH2 (Notch 2) • MSH3 (MutS Homolog 3) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • FCGR3A (Fc Fragment Of IgG Receptor IIIa) • CHD4 (Chromodomain Helicase DNA Binding Protein 4) • HNF1A (HNF1 Homeobox A)
|
KMT2C mutation • MLL3 deletion • MLL3 mutation
|
Keytruda (pembrolizumab) • Opdivo (nivolumab)
2years
Mutations in lysine methyltransferase 2C and PEG3 are associated with tumor mutation burden, prognosis, and antitumor immunity in pancreatic adenocarcinoma patients. (PubMed, Digit Health)
Meanwhile, significant differences in the composition of the immune cells were observed for KMT2C and PEG3 mutations PAAD patients, for providing additional guidelines for antitumor treatments in various KMT2C and PEG3 mutation states in PAAD. This study reveals that KMT2C and PEG3 mutation may serve as biomarkers for predicting prognosis and guiding anti-PAAD immunotherapy for PAAD patients.
Journal • Tumor Mutational Burden • IO biomarker
|
TMB (Tumor Mutational Burden) • KMT2C (Lysine Methyltransferase 2C)
|
TMB-H • KMT2C mutation • MLL3 mutation
2years
Clinical profiling and comprehensive analysis of candidate genes related to breast cancer estrogen receptor intratumour heterogeneity (SABCS 2022)
We identified the mutation in codon 321 was the hot spot of KMT2C in our patient cohort.Next, we used the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to analyze the enriched pathways of KMT2C. KEGG pathway analysis revealed that patients with KMT2C mutations harbored significantly more mutations in genes involved in the Ubiquitin mediated proteolysis and Lysine degradation signaling pathway.
Clinical
|
ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • KMT2C (Lysine Methyltransferase 2C)
|
TP53 mutation • PIK3CA mutation • KMT2C mutation • TP53 expression • MLL3 mutation
|
FoundationOne® CDx
2years
CARM1-mediated methylation of ASXL2 impairs tumor-suppressive function of MLL3/COMPASS. (PubMed, Sci Adv)
ASXL2 methylation blocks binding to MLL3 and impairs the expression of MLL3/COMPASS-dependent genes. This previously unidentified transcriptional repressive function of CARM1 provides insight into the BAP1/MLL3-COMPASS axis and reveals a potential cancer therapeutic target.
Journal • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BAP1 (BRCA1 Associated Protein 1) • KMT2C (Lysine Methyltransferase 2C)
|
BAP1 mutation • MLL3 mutation
2years
Multi-omics analysis defines highly refractory RAS burdened immature subgroup of infant acute lymphoblastic leukemia. (PubMed, Nat Commun)
Importantly, our deep mutational analysis reveals that the number of RAS pathway mutations predicts prognosis and that the most refractory subgroup of IC2 possesses 100% frequency and the heaviest burden of RAS pathway mutations. Our findings highlight the previously under-appreciated intra- and inter-patient heterogeneity of KMT2A-rearranged infant ALL and provide a rationale for the future development of genomics-guided risk stratification and individualized therapy.
Journal
|
KMT2A (Lysine Methyltransferase 2A) • AFF1 (AF4/FMR2 Family Member 1) • MLLT3 (MLLT3 Super Elongation Complex Subunit)
|
RAS mutation • MLL rearrangement • MLL3 mutation
over2years
KMT2C mutation in a Chinese man with primary multidrug-resistant metastatic adenocarcinoma of rete testis: a case report. (PubMed, BMC Urol)
A potential correlation between AORT primary multi-drug resistance and KMT2C mutations is implied. Further studies are needed to determine the efficacy of PARP1/2 inhibitors for tumors with KMT2C mutations.
Journal • PARP Biomarker
|
KMT2C (Lysine Methyltransferase 2C)
|
KMT2C mutation • MLL3 mutation