Lynch syndrome is the most common inherited colon cancer syndrome. Patients with Lynch syndrome develop a range of cancers including colorectal cancer (CRC) and carry a mutation on one of the mismatched repair (MMR) genes. Although CRC usually occurs after the fourth decade in patients with Lynch syndrome harboring a heterozygous MMR gene mutation, it can occur in children with Lynch syndrome w...

Mismatch repair (MMR)-deficient cells are shown to produce >15-fold more methotrexate-resistant colonies than MMR normal cells. The increased resistance to methotrexate is primarily due to gene amplification since all the resistant clones contain double-minute chromosomes and increased copy numbers of the DHFR gene. In addition, integration of linearized or retroviral DNAs into chromosomes is a...

Mismatch (MMR) repair system plays a significant role in restoration of stability in the genome. Mutations in mismatch repair genes hamper their activity thus bring about a defect in mismatch repair (MMR) mechanism thereby conferring instability in the microsatellite sequences of both the coding and non-coding regions of the genome. Mutated mismatch repair genes result in the expansion or contr...

A pooled analysis was conducted of 1257 toddlers who received a fourth dose of Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) or Hib conjugate vaccine (Hib polysaccharide conjugated to N. meningitidis outer membrane protein) coadministered with measles-mumps-rubella (MMR) and varicella (VAR) vaccines (NCT00134719/NCT0028978...

Media attention and consequent public concerns about vaccine safety followed publication of a small case-series of children who developed autism after receipt of the measles-mumps-rubella (MMR) vaccine. Many well-controlled studies performed subsequently found no evidence that MMR vaccine causes autism. However, despite these studies, some parents remain concerned that the MMR vaccine is not sa...

A considerable surge of interest in the mismatch repair (MMR) system has been brought about by the discovery of a link between Lynch syndrome, an inherited predisposition to cancer of the colon and other organs, and malfunction of this key DNA metabolic pathway. This review focuses on recent advances in our understanding of the molecular mechanisms of canonical MMR, which improves replication f...

The identification of germline variants predisposing to hereditary nonpolyposis colorectal cancer (HNPCC) is crucial for clinical management of carriers, but several probands remain negative for such variants or bear variants of uncertain significance (VUS). Here we describe the results of integrative molecular analyses in 132 HNPCC patients providing evidences for improved genetic testing of H...

BACKGROUND Colorectal cancer (CRC) represents a morphologic and molecular heterogenic disease. This heterogeneity substantially impairs drug effectiveness and prognosis. The subtype of mismatch repair deficient (MMR-D) CRCs, accounting for about 15% of all cases, shows particular differential responses up to resistance towards currently approved cytostatic drugs. Pre-clinical in vitro models re...

Loss of a functional mismatch repair (MMR) system in colorectal cancer (CRC) cells is associated with microsatellite instability and increased sensitivity to topoisomerase inhibitors. In this study, we have investigated whether a defect in double-strand break (DSB) repair by non-homologous end-joining (NHEJ) could explain why MMR-deficient CRC cells are hypersensitive to camptothecin (CPT), a t...

Variations in mismatch repair (MMR) system genes are causative of Lynch syndrome and other cancers. Thousands of variants have been identified in MMR genes, but the clinical relevance is known for only a small proportion. Recently, the InSiGHT group classified 2,360 MMR variants into five classes. One-third of variants, majority of which is nonsynonymous variants, remain to be of uncertain clin...