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

    MSH3 mutation

    i
    Other names: MSH3, MutS Homolog 3, Divergent Upstream Protein, Mismatch Repair Protein 1, DNA Mismatch Repair Protein Msh3, HMSH3, MRP1, DUP, Epididymis Secretory Sperm Binding Protein, MutS (E. Coli) Homolog 3, MutS Homolog 3 (E. Coli), FAP4, DUC1, DUG
    Entrez ID:
    4437
    Related biomarkers:
    Expression
    1year
    UBASH3B-mediated MRPL12 Y60 dephosphorylation inhibits LUAD development by driving mitochondrial metabolism reprogramming. (PubMed, J Exp Clin Cancer Res)
    This study establishes MRPL12 as a novel oncogene in LUAD, contributing to LUAD pathogenesis by orchestrating mitochondrial metabolism reprogramming towards oxidative phosphorylation (OXPHOS). Furthermore, it confirms Y60 as a specific phosphorylation modification site regulating MRPL12's oncogenic functions, offering insights for the development of LUAD-specific targeted drugs and clinical interventions.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS G12D • KRAS G12 • MSH3 mutation • KRAS deletion
    over1year
    Microsatellite instability in mismatch repair proficient colorectal cancer: clinical features and underlying molecular mechanisms. (PubMed, EBioMedicine)
    This study revealed pMMR/MSI-H CRC as a distinct subgroup within CRC, which manifests diverse clinicopathological features and long-term prognostic outcomes. Distinct features in the tumour immune-microenvironment were observed in pMMR/MSI-H CRCs. Pathogenic deleterious mutations in MSH3-K383fs were frequently detected, suggesting another potential biomarker for identifying MSI-H.
    Journal • Mismatch repair • Microsatellite instability • MSi-H Biomarker
    |
    MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • MSH3 (MutS Homolog 3)
    |
    MSI-H/dMMR • MSH3 mutation
    almost2years
    GC 2nd Line Durvalumab(MEDI4736)/Tremelimumab Plus Paclitaxel Study (clinicaltrials.gov)
    P1/2, N=58, Completed, Asan Medical Center | Active, not recruiting --> Completed
    Trial completion
    |
    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • POLD1 (DNA Polymerase Delta 1) • MSH3 (MutS Homolog 3) • PMS1 (PMS1 protein homolog 1) • POLD2 (DNA Polymerase Delta 2)
    |
    MSI-H/dMMR • MSH2 mutation • MLH1 mutation • PD-L1 amplification • POLD1 mutation • MSH3 mutation • PMS2 mutation • MLH3 mutation • PMS1 mutation • POLD2 mutation
    |
    Imfinzi (durvalumab) • paclitaxel • Imjudo (tremelimumab-actl)
    almost2years
    Identification and characterization of immunogenic neoantigens in colorectal cancer (CRC). (ASCO-GI 2024)
    This is one of the largest studies to investigate the landscape of immunogenic neoantigens in CRC. We were able to identify candidate recurrent peptides with high HLA binding affinity and an association with a positive TIS signature supporting the role of neoantigens as potential cancer immunotherapy targets.
    MSi-H Biomarker • IO biomarker
    |
    MSI (Microsatellite instability) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2D (Lysine Methyltransferase 2D) • RNF43 (Ring Finger Protein 43) • APC (APC Regulator Of WNT Signaling Pathway) • MSH3 (MutS Homolog 3) • SOX9 (SRY-Box Transcription Factor 9)
    |
    MSI-H/dMMR • APC mutation • RNF43 mutation • MSH3 mutation
    over2years
    Pan-cancer association of DNA repair deficiencies with whole-genome mutational patterns. (PubMed, Elife)
    CDK12 is associated with tandem-duplications, and we here demonstrate that this association can accurately predict gene deficiency in prostate cancers (area under the ROC curve=0.97). Our novel associations include mono- or biallelic LOF variants of ATRX, IDH1, HERC2, CDKN2A, PTEN, and SMARCA4, and our systematic approach yielded a catalogue of predictive models, which may provide targets for further research and development of treatment, and potentially help guide therapy.
    Journal • BRCA Biomarker • PARP Biomarker • Pan tumor
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDK12 (Cyclin dependent kinase 12) • ATRX (ATRX Chromatin Remodeler) • MSH3 (MutS Homolog 3) • DRD (DNA Repair Deficiency)
    |
    TP53 mutation • BRCA2 mutation • BRCA1 mutation • DDR • CDK12 mutation • MSH3 mutation • DRD
    almost3years
    GC 2nd Line Durvalumab(MEDI4736)/Tremelimumab Plus Paclitaxel Study (clinicaltrials.gov)
    P1/2, N=58, Active, not recruiting, Asan Medical Center | Unknown status --> Active, not recruiting | Trial completion date: Jun 2021 --> Jun 2023 | Trial primary completion date: Jun 2021 --> Jun 2023
    Enrollment closed • Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • POLD1 (DNA Polymerase Delta 1) • MSH3 (MutS Homolog 3) • PMS1 (PMS1 protein homolog 1) • POLD2 (DNA Polymerase Delta 2)
    |
    MSI-H/dMMR • MSH2 mutation • MLH1 mutation • PD-L1 amplification • POLD1 mutation • MSH3 mutation • PMS2 mutation • MLH3 mutation • PMS1 mutation • POLD2 mutation
    |
    Imfinzi (durvalumab) • paclitaxel • Imjudo (tremelimumab-actl)
    almost3years
    Analysis of Concordance Between NGS-MSI and IHC-MMR from 180,000 Solid Tumors (USCAP 2023)
    Analysis of 180,000 tumors revealed a high concordance of IHC-MMR/NGS-MSI with a rate of 99.7%. In 20% of MMRp/MSI-H cases, interpretation of IHC lead to misdiagnosis that the NGS-MSI would have avoided. Clinical outcome from a large cohort of patients show NGS is not inferior compared to IHC in identifying patients with MSI-H/MMRd.
    MSi-H Biomarker • IO biomarker • Next-generation sequencing • Discordant
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • MSH3 (MutS Homolog 3) • PMS1 (PMS1 protein homolog 1)
    |
    MSI-H/dMMR • MSH2 mutation • MLH1 mutation • MSH3 mutation • PMS2 mutation • MLH3 mutation • PMS1 mutation
    |
    MI Tumor Seek™
    almost3years
    Analysis of concordance between microsatellite instability by next generation sequencing (NGS-MSI) and mismatch repair deficiency by immunohistochemistry (IHC-MMR) in >28,000 colorectal tumors. (ASCO-GI 2023)
    Here we report from >28,000 CRC tumors that the concordance of IHC-MMR/NGS-MSI is 99.74%. Clinical outcome from a large cohort of patients show NGS is not inferior compared to IHC in identifying patients with MSI-H/MMRd. The additional lens that NGS-MSI offers is of value in identifying CRC patients who may benefit from ICI therapy.
    Next-generation sequencing • Mismatch repair • Microsatellite instability • MSi-H Biomarker • IO biomarker • Discordant
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • MSH3 (MutS Homolog 3) • PMS1 (PMS1 protein homolog 1)
    |
    MSI-H/dMMR • MSH2 mutation • MLH1 mutation • MSH3 mutation • PMS2 mutation • MLH3 mutation • PMS1 mutation
    3years
    Individualized combination therapies based on whole-exome sequencing displayed significant clinical benefits in a glioblastoma patient with secondary osteosarcoma: case report and genetic characterization. (PubMed, BMC Neurol)
    Individualized combination therapies based on whole-exome sequencing displayed significant clinical benefits in this case. Germline MSH3 and ERCC4 mutation may induce a secondary osteosarcoma in glioblastoma patients.
    Journal • Combination therapy • PD(L)-1 Biomarker
    |
    PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase) • CDH1 (Cadherin 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • EPAS1 (Endothelial PAS domain protein 1) • MSH3 (MutS Homolog 3) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit)
    |
    NF1 mutation • TERT mutation • MSH3 mutation • IDH wild-type • SETD2 mutation • ERCC4 mutation
    |
    Keytruda (pembrolizumab) • everolimus • temozolomide