Function MSH2 can bind to MSH6 or to MSH3 to form the MutS alpha or the MutS beta complexes respectively. While MutS alpha complex binds to base-base and insertion-deletion mismatches, MutS beta only binds to insertion-deletion mismatches. Upon binding to the mismatch, the MutS complex associates with the MutL complex (composed of MLH1 and PMS2), and recruits the proteins needed for DNA excisio...

Epigenetic silencing of tumour suppressor genes has been observed in various cancers. Looking at hepatocellular carcinoma (HCC) specific protein silencing was previously demonstrated to be associated with the Hepatitis C virus (HCV). However, the proposed HCV dependent promoter methylation of DNA mismatch repair (MMR) genes and thereby enhanced progression of hepatocarcinogenesis has been the s...

Interference-dependent crossing over in yeast and mammalian meioses involves the mismatch repair protein homologs MSH4-MSH5 and MLH1-MLH3. The MLH3 protein contains a highly conserved metal binding motif DQHA(X)2E(X)4E that is found in a subset of MLH proteins predicted to have endonuclease activities (KADYROV et al. 2006). Mutations within this motif in human PMS2 and S. cerevisiae PMS1 disrup...

Abstract Multiple large-scale genomic studies across pediatric tumors have reported an overall frequency of ~6-10% patients with constitutional pathogenic variants, but associations cancer predisposition distinct tumor types vary between zero and 100%. We analyzed sequencing DNA methylation data from 363 to explore the landscape in high-grade gliomas (pedHGG). Almost all pedHGG alterations resu...

Similar to other anticancer agents, intrinsic or acquired resistance to DNA-damaging chemotherapeutics is a major obstacle for cancer therapy. Current strategies aimed at overcoming this problem are mostly based on the premise that tumor cells acquire heritable genetic mutations that contribute to drug resistance. Here, we present evidence for an epigenetic, tumor cell adhesion-mediated, and re...

Objective Although the utility of immunohistochemistry (IHC) for assessing mismatch repair (MMR) protein expression has been demonstrated in solid tumors including primary prostate cancer (PCa), its utility has not been assessed in castration-resistant PCa (CRPC). Methods Tissue microarrays were constructed from 127 radical prostatectomies and 155 CRPC metastases from 50 patients. MMR (MLH1, ...

Lynch syndrome is the most common form of hereditary colorectal cancer and is caused by germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. Mutation carriers have an increased lifetime risk of developing colorectal cancer as well as other extracolonic tumours. The aim of the current study was to evaluate the frequency and distribution of mutations in the MLH1, MSH2 ...

Lynch syndrome (LS) is one of the most common familial forms of colorectal cancer predisposing syndrome with an autosomal dominant mode of inheritance. LS is caused by the germline mutations in DNA mismatch repair (MMR) genes including MSH2, MLH1, MSH6 and PMS2. Clinically, LS is characterized by high incidence of early-onset colorectal cancer as well as endometrial, small intestinal and urinar...

Microsatellite instable gastric cancer (MSI-GC) is a specific molecular subtype of GC. We studied the phenotypes, genotypes, and clinicopathologic characteristics of MSI-GC in a white GC cohort and compared our findings with an extended literature review. The study cohort consisted of 482 patients. Specimens were available from 452 cases and were used for immunostaining (MLH1, PMS2, MSH2, MSH6)...

Single nucleotide polymorphisms (SNPs) in mismatch repair genes, especially in the MLH1 gene, are closely associated with susceptibility to hereditary nonpolyposis colorectal cancer. However, few relevant findings are available regarding the association between sporadic colorectal cancer (SCRC) and SNPs of MLH1 in Chinese patients. Therefore, the present study aimed to describe the pathogenic a...