Aim The aim of this study was to evaluate the methylation status of the promoter region of MLH1 gene in colorectal cancer (CRC) and its precursor lesions as well as elucidate its association with various clinicopathological characteristics among Iranian population. Background Epigenetic silencing of mismatch repair genes, such as MLH1, by methylation of CpG islands of their promoter region ha...

Germline mutations in the DNA mismatch repair genes MSH2 and MLH1 are responsible for the majority of hereditary nonpolyposis colorectal cancer (HNPCC) families. A common mutation mechanism is to disrupt MLH1 and MSH2 mRNA splicing. The disruption creates aberrant mRNAs lacking specific coding exons (exon skipping). Here, we report a novel skipping of MLH1 exon 12 caused by an AAG to TAG nonsen...

Epidemiological data demonstrated that hormone replace treatment has protective effect against colorectal cancer (CRC). Our previous studies showed that this effect may be associated with DNA mismatch repair. This study aims to investigate the mechanism of estrogen induction of MLH1, and whether colorectal tumor proliferation can be inhibited through induction of MLH1 by estrogen signal pathway...

An accurate algorithm is essential for effective molecular diagnosis of hereditary colorectal cancer (CRC). Here, we have extended the analysis of 71 CRC cases suspected to be Lynch syndrome cases for MSH2, MLH1, MSH6, and PMS2 gene defects. All cases were screened for mutations in MSH2, MLH1, and MSH6, and all cases where tumors were available were screened for microsatellite instability (MSI)...

PURPOSE Little information is available on genetic and epigenetic changes in duodenal adenocarcinomas. The purpose was to identify possible subsets of duodenal adenocarcinomas based on microsatellite instability (MSI), DNA methylation, mutations in the KRAS and BRAF genes, clinicopathologic features, and prognosis. EXPERIMENTAL DESIGN Demographics, tumor characteristics, and survival were ava...

Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson-Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot's syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structur...

Lynch syndrome (hereditary nonpolypsis colorectal cancer or HNPCC) is a common cancer predisposition syndrome. Predisposition to cancer in this syndrome results from increased accumulation of mutations due to defective mismatch repair (MMR) caused by a mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2/scPMS1. To better understand the function of Mlh1-Pms1 in MMR, we used Sac...

Crossing over between homologs is initiated in meiotic prophase by the formation of DNA double-strand breaks that occur throughout the genome. In the major interference-responsive crossover pathway in baker's yeast, these breaks are resected to form 3' single-strand tails that participate in a homology search, ultimately forming double Holliday junctions (dHJs) that primarily include both homol...

We describe a new approach to investigate alterations in the human MLH1 mismatch repair (MMR) gene. This is based on complementation of the phenotype of a MLH1-defective subclone of the ovarian carcinoma A2780 cells by transfection of vectors encoding altered MLH1 proteins. Measurements of resistance (tolerance) to methylating agents, mutation rate at HPRT, microsatellite instability (MSI), and...

The mutL homolog-1 (MLH1) is a DNA mismatch repair gene and has been reported to be frequently methylated in numerous cancers. However, the association between MLH1 methylation and esophageal cancer (EC), as well as its clinical significance, remains unclear. Hence, we conducted a systematic meta-analysis based on 19 articles (including 1384 ECs, 345 premalignant lesions, and 1244 healthy contr...