Search results for "MSH6"
showing 10 items of 15 documents
Uptake of hysterectomy and bilateral salpingo-oophorectomy in carriers of pathogenic mismatch repair variants:a Prospective Lynch Syndrome Database r…
2021
Purpose: This study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants.Methods: The Prospective Lynch Syndrome Database (PLSD) was used to investigate RRS by a cross-sectional study in 2292 female path_MMR carriers aged 30-69 years.Results: Overall, 144, 79, and 517 carriers underwent risk-reducing hysterectomy, BSO, or both combined, respectively. Two-thirds of procedures before 50 years of age were combined hysterectomy and BSO, and 81% of all procedures included BSO. Risk-reducing hysterectomy was performed before age 50 years in 28%, 25%,…
Molecular Basis of Mismatch Repair Protein Deficiency in Tumors from Lynch Suspected Cases with Negative Germline Test Results
2020
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Easy One-Step Amplification and Labeling Procedure for Copy Number Variation Detection.
2019
Abstract Background The specific characteristics of copy number variations (CNVs) require specific methods of detection and characterization. We developed the Easy One-Step Amplification and Labeling procedure for CNV detection (EOSAL-CNV), a new method based on proportional amplification and labeling of amplicons in 1 PCR. Methods We used tailed primers for specific amplification and a pair of labeling probes (only 1 labeled) for amplification and labeling of all amplicons in just 1 reaction. Products were loaded directly onto a capillary DNA sequencer for fragment sizing and quantification. Data obtained could be analyzed by Microsoft Excel spreadsheet or EOSAL-CNV analysis software. We d…
Associations of Pathogenic Variants in MLH1, MSH2, and MSH6 With Risk of Colorectal Adenomas and Tumors and With Somatic Mutations in Patients With L…
2020
Contains fulltext : 220040.pdf (Publisher’s version ) (Closed access) BACKGROUND & AIMS: Lynch syndrome is caused by variants in DNA mismatch repair (MMR) genes and associated with an increased risk of colorectal cancer (CRC). In patients with Lynch syndrome, CRCs can develop via different pathways. We studied associations between Lynch syndrome-associated variants in MMR genes and risks of adenoma and CRC and somatic mutations in APC and CTNNB1 in tumors in an international cohort of patients. METHODS: We combined clinical and molecular data from 3 studies. We obtained clinical data from 2747 patients with Lynch syndrome associated with variants in MLH1, MSH2, or MSH6 from Germany, the Net…
Benzo[a]pyrene represses DNA repair through altered E2F1/E2F4 function marking an early event in DNA damage-induced cellular senescence
2020
AbstractTranscriptional regulation of DNA repair is of outmost importance for the restoration of DNA integrity upon genotoxic stress. Here we report that the potent environmental carcinogen benzo[a]pyrene (B[a]P) activates a cellular DNA damage response resulting in transcriptional repression of mismatch repair (MMR) genes (MSH2, MSH6, EXO1) and of RAD51, the central homologous recombination repair (HR) component, ultimately leading to downregulation of MMR and HR. B[a]P-induced gene repression is caused by abrogated E2F1 signalling. This occurs through proteasomal degradation of E2F1 in G2-arrested cells and downregulation of E2F1 mRNA expression in G1-arrested cells. Repression of E2F1-me…
Nuclear Translocation of Mismatch Repair Proteins MSH2 and MSH6 as a Response of Cells to Alkylating Agents
2000
Mammalian mismatch repair has been implicated in mismatch correction, the prevention of mutagenesis and cancer, and the induction of genotoxicity and apoptosis. Here, we show that treatment of cells specifically with agents inducing O(6)-methylguanine in DNA, such as N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea, elevates the level of MSH2 and MSH6 and increases GT mismatch binding activity in the nucleus. This inducible response occurs immediately after alkylation, is long-lasting and dose-dependent, and results from translocation of the preformed MutSalpha complex (composed of MSH2 and MSH6) from the cytoplasm into the nucleus. It is not caused by an increase in MSH2 gen…
Involvement of large rearrangements in MSH6 and PMS2 genes in southern Italian patients with lynch syndrome
2018
Background and aim of the work: The Lynch Syndrome (LS) is associated with germline mutations in one of the MisMatch Repair (MMR) genes. Most of germline mutations are point variants, followed by large rearrangements that account to 15-55% of all pathogenic mutations. Many study reporting the frequency of large rearrangements in the MLH1 and MSH2 genes were performed, while, little is known about the contribution of large rearrangements in other MMR genes, as PMS2 and MSH6. Therefore, in this study we investigated the involvment of large rearrangements in MSH6 and PMS2 genes in a well-characterized series of 20 LS southern Italian patients. Methods: These large rearrangements are not usuall…
Identification of New Genetic Clusters in Glioblastoma Multiforme: EGFR Status and ADD3 Losses Influence Prognosis
2020
Glioblastoma multiforme (GB) is one of the most aggressive tumors. Despite continuous efforts to improve its clinical management, there is still no strategy to avoid a rapid and fatal outcome. EGFR amplification is the most characteristic alteration of these tumors. Although effective therapy against it has not yet been found in GB, it may be central to classifying patients. We investigated somatic-copy number alterations (SCNA) by multiplex ligation-dependent probe amplification in a series of 137 GB, together with the detection of EGFRvIII and FISH analysis for EGFR amplification. Publicly available data from 604 patients were used as a validation cohort. We found statistical associations…
Prognostic Role of Mismatch Repair Status, Histotype and High-Risk Pathologic Features in Stage II Small Bowel Adenocarcinomas
2020
Abstract Background Small bowel adenocarcinoma is a relatively rare cancer, often diagnosed in an advanced stage. In localized and resectable disease, surgery alone or in combination with adjuvant chemotherapy is the mainstay of treatment. In the recently published National Comprehensive Cancer Network Clinical Practice guidelines, criteria for selecting patients with stage II small bowel adenocarcinoma to receive adjuvant chemotherapy are provided, and they are mainly extrapolated from studies on colorectal cancer. Patients and Methods In the present study, we aimed to verify whether mismatch repair deficiency phenotype, high-risk pathologic features (including T4, positive resection margi…
Contribution of Large Genomic Rearrangements in Italian Lynch Syndrome Patients: Characterization of a Novel Alu-Mediated Deletion
2012
Lynch syndrome is associated with germ-line mutations in the DNA mismatch repair (MMR) genes, mainlyMLH1andMSH2. Most of the mutations reported in these genes to date are point mutations, small deletions, and insertions. Large genomic rearrangements in the MMR genes predisposing to Lynch syndrome also occur, but the frequency varies depending on the population studied on average from 5 to 20%. The aim of this study was to examine the contribution of large rearrangements in theMLH1andMSH2genes in a well-characterised series of 63 unrelated Southern Italian Lynch syndrome patients who were negative for pathogenic point mutations in theMLH1,MSH2, andMSH6genes. We identified a large novel delet…