News - MSH6 mutation - LARVOL VERI

11ms

Mismatch repair (MMR) and microsatellite instability (MSI) phenotypes across solid tumors: A comprehensive cBioPortal study on prevalence and prognostic impact. (PubMed, Eur J Cancer)

MMR-m GECs showed improved overall survival compared to MMR-wt (p = 0.009), a relationship not observed in other tumor types. This study demonstrates that the MMR spectrum is extremely hetoerogeneous in solid tumors, highliting the need for comprehensive and tumor-specific testing strategies.

11 months ago

Journal • Mismatch repair • Microsatellite instability

MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)

MSH6 mutation • MSH2 mutation • PMS2 mutation

1year

Germline mismatch repair gene mutations in children with tumors: a case series from two centers. (PubMed, Transl Pediatr)

A better diagnostic approach is to perform genetic testing to rule out the risk as early as possible when a newborn presents with cafe-au-lait spots, which are a typical feature of hereditary syndromes. Therefore, it is important to use germline genetic testing, combined with clinical phenotypic observation, to establish a diagnosis of a cancer susceptibility syndrome caused by an MMR gene mutation.

1 year ago

Journal • Mismatch repair

NF1 (Neurofibromin 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)

MSH6 mutation • MSH2 mutation • MLH1 mutation

over1year

Mitotic abnormalities precede microsatellite instability in lynch syndrome-associated colorectal tumourigenesis. (PubMed, EBioMedicine)

The results validate our previous findings from mice and highlight early mitotic abnormalities as an important contributor and precancerous marker of colorectal tumourigenesis in LS.

over 1 year ago

Journal • Microsatellite instability

MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)

MSH6 mutation • MSH2 mutation • MLH1 mutation

almost2years

Mismatch repair gene MSH6 correlates with the prognosis, immune status and immune checkpoint inhibitors response of endometrial cancer. (PubMed, Front Immunol)

Reduced MSH6 expression could serve as a potential biomarker for predicting better prognosis, active immune status, higher immune checkpoint expression level and better responsiveness to ICIs treatment in EC. MSH6 may become a potential target for treating solid tumors.

almost 2 years ago

Journal • Checkpoint inhibition • Mismatch repair • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • MSH6 (MutS homolog 6) • PD-L2 (Programmed Cell Death 1 Ligand 2)

PD-L1 expression • MSH6 mutation • PD-L2 expression • MSH6 expression

almost2years

Endometrial Cancers with Low Level Microsatellite Instability: Classification Pitfalls and Practical Recommendations for Assigning Mismatch Repair Status by Next Generation Sequencing with MSIsensor and Ancillary Tests (USCAP 2024)

MSIsensor scores as low as 3.5% may represent true MMRd in EC tested by NGS. Further testing for MMRd is advised for MSIsensor scores between 3% and 30%, particularly if there is low tumor content or associated high TMB. In this setting, MMR IHC may have superior sensitivity for detection of MMRd compared to DNA-based assays.

almost 2 years ago

Microsatellite instability • Tumor mutational burden • IO biomarker • Next-generation sequencing • Mismatch repair

TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)

TMB-H • POLE mutation • MSH6 mutation • MSH2 mutation • PMS2 mutation

Idylla™ MSI Test

almost2years

Rare germline mutation and MSH2-&MSH6 + expression in a double primary carcinoma of colorectal carcinoma and endometrial carcinoma: a case report. (PubMed, Diagn Pathol)

In the case of a patient with double primary EC and CRC, a careful evaluation of the IHC and the genetic data was presented. The patient carried rare compound heterozygous variants, a germline missense mutation, and a somatic frameshift mutation of MSH6, combined with a novel somatic null variant of MSH2. Our study broadened the variant spectrum of double primary cancer and provided insight into the molecular basis for abnormal MSH2 protein loss and double primary carcinoma.

almost 2 years ago

Journal

MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • EPCAM (Epithelial cell adhesion molecule)

MSI-H/dMMR • MSH6 mutation • MSH2 mutation

almost2years

Rise of oligodendroglioma hypermutator phenotype from a subclone harboring TP53 mutation after TMZ treatment. (PubMed, Brain Tumor Pathol)

This case embodied the theoretically understandable clonal expansion of the TP53 mutation with additional mismatch repair gene dysfunction leading to hypermutator phenotype. It thus indicated that TP53 mutation in oligodendroglioma, although not common, may play a critical role in the development of hypermutator after TMZ treatment.

almost 2 years ago

Journal

TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • MSH6 (MutS homolog 6)

TP53 mutation • IDH1 mutation • MSH6 mutation • TP53 R248Q

almost2years

Molecular and clinical characteristics of POLE/POLD1 alterations among patients with colorectal cancer. (ASCO-GI 2024)

POLE/POLD1 mutations frequently co-exist with MSI-H disease in CRC. Patients with MSS-CRC harboring POLE/POLD1 mutations represent a smaller subgroup of CRC (~1%). The incidence of POLE/POLD1 somatic mutations was more common among patients with colon cancer than those with rectal cancer.

almost 2 years ago

Clinical • MSi-H Biomarker

MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • POLD1 (DNA Polymerase Delta 1)

MSI-H/dMMR • POLE mutation • MSH6 mutation • MSH2 mutation • MLH1 mutation • POLD1 mutation • PMS2 mutation • POLE mutation + POLD1 mutation

almost2years

Liquid biopsy-based comprehensive genomic profiling to reveal mutational landscape in real-world patients with gastrointestinal cancer. (ASCO-GI 2024)

This study elucidated the comprehensive mutational landscape of advanced gastrointestinal cancer through liquid biopsy, thereby contributing novel biomarkers for clinical diagnosis and facilitating targeted therapy mechanism investigations.

almost 2 years ago

Real-world evidence • Clinical • Tumor mutational burden • BRCA Biomarker • Liquid biopsy • Real-world • Biopsy

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • MLH1 (MutL homolog 1) • FGFR4 (Fibroblast growth factor receptor 4) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • FAT1 (FAT atypical cadherin 1) • EPCAM (Epithelial cell adhesion molecule) • ERCC5 (ERCC Excision Repair 5 Endonuclease 2)

EGFR mutation • HRD • MSH6 mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation

PredicineCARE™

2years

Diffuse Large B-Cell Lymphoma Has a Low Frequency of dMMR and High Frequencies of DNA Mismatch Repair Protein High Expression Associated with Lower T-Cell Infiltration (ASH 2023)

This study revealed that high expression of MMR proteins is a common feature of DLBCL associated with lower tumor-infiltrating T cells, MYC and p53 overexpression, and context-dependent prognostic effects. In contrast, dMMR and loss of MMR proteins are infrequent and have no significant prognostic effects in DLBCL treated with standard chemoimmunotherapy. These results may have implications for understanding DLBCL biology and the low efficacy of PD-1 blockade immunotherapy in DLBCL.

2 years ago

Mismatch repair • PD(L)-1 Biomarker • IO biomarker

MSI (Microsatellite instability) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)

MSI-H/dMMR • MYC overexpression • MYC expression • MSH6 mutation • MLH1 mutation • PMS2 mutation • TP53 overexpression • MSH6 expression

2years

Cisplatin-induced DNA crosslinks trigger neurotoxicity in C. elegans. (PubMed, Biochim Biophys Acta Mol Cell Res)

To conclude, we provide evidence that neurotoxicity, including sensory neurotoxcity, is triggered by CisPt-induced DNA intra- and interstrand crosslinks that are subject of repair by NER and ICL repair. We hypothesize that especially ERCC1/XPF, CSB and MSH6-related DNA repair protects from chemotherapy-induced neuropathy in the context of CisPt-based anticancer therapy.

2 years ago

Journal

MSH6 (MutS homolog 6) • ERCC1 (Excision repair cross-complementation group 1) • XPC (XPC Complex Subunit, DNA Damage Recognition And Repair Factor) • ANO1 (Anoctamin 1)

MSH6 mutation

cisplatin

2years

A Comprehensive Study of Heterogeneous Mismatch Repair Expression in Solid Tumors Reveals Different Immunohistochemical Patterns and Distinct Genetic Mechanisms. (PubMed, Am J Surg Pathol)

Our findings highlighted the importance of accurately interpreting heterogeneous MMR protein staining patterns for developing a more efficient personalized genetic investigation strategy.

2 years ago

Journal • Mismatch repair • Tumor mutational burden

TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)

TMB-H • POLE mutation • MSH6 mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation • POLE EDM