Malignant astrocytomas are the most aggressive primary brain tumors with a poor prognosis despite optimal treatment. Dysfunction of mismatch repair (MMR) system accelerates the accumulation of mutations throughout the genome causing uncontrolled cell growth. The aim of this study was to characterize the MMR system defects that could be involved in malignant astrocytoma pathogenesis. We analyzed...

DNA double-strand breaks (DSBs) must be accurately repaired to maintain genomic integrity. DSBs can be repaired by homologous recombination (HR), which uses an identical sequence as a template to restore the genetic information lost at the break. Suppression of recombination between diverged sequences is essential to the repair of DSBs without aberrant and potentially mutagenic recombination be...

The fragile X-related disorders result from expansion of a CGG/CCG microsatellite in the 5' UTR of the FMR1 gene. We have previously demonstrated that the MSH2/MSH3 complex, MutSβ, that is important for mismatch repair, is essential for almost all expansions in a mouse model of these disorders. Here we show that the MSH2/MSH6 complex, MutSα also contributes to the production of both germ line a...

BACKGROUND Despite their histological resemblance to colorectal adenocarcinomas, there is little information about the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinomas (ITACs). AIMS To evaluate the possible role of DNA mismatch repair (MMR) gene defects or disruptions of the E cadherin-beta catenin complex in ITAC by investigating the immunohistochemi...

Recombination between moderately divergent DNA sequences is impaired compared with identical sequences. In yeast, an HO endonuclease-induced double-strand break can be repaired by single-strand annealing (SSA) between flanking homologous sequences. A 3% sequence divergence between 205-bp sequences flanking the double-strand break caused a 6-fold reduction in repair compared with identical seque...

Biallelic germline mutations in the mismatch repair genes, including MLH1, MSH2, MSH6 or PMS2, lead to a recessive constitutional mismatch repair-deficiency (CMMR-D) syndrome characterized by early onset malignancies in children and young adults. Because consanguinity unmasks autosomal recessive disorders, we hypothesized that the frequency of CMMR-D is inflated in the highly consanguineous pop...

Malignant gliomas have a very poor prognosis. The current standard of care for these cancers consists of extended adjuvant treatment with the alkylating agent temozolomide after surgical resection and radiotherapy. Although a statistically significant increase in survival has been reported with this regimen, nearly all gliomas recur and become insensitive to further treatment with this class of...

Lynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 p...

A change in the number of base pairs within a coding sequence can result in a frameshift mutation, which almost invariably eliminates the function of the encoded protein. A frameshift reversion assay with Saccharomyces cerevisiae that can be used to examine the types of insertions and deletions that are generated during DNA replication, as well as the editing functions that remove such replicat...