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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Cellular DNA damage caused by reactive oxygen species is repaired by the base excision repair (BER) pathway which includes the DNA glycosylase MUTYH. Inherited biallelic MUTYH mutations cause predisposition to colorectal adenomas and carcinoma. However, the mechanistic progression from germline MUTYH mutations to MUTYH-Associated Polyposis (MAP) is incompletely understood. Here, we sequence normal tissue DNAs from 10 individuals with MAP. Somatic base substitution mutation rates in intestinal epithelial cells were elevated 2 to 4-fold in all individuals, except for one showing a 31-fold increase, and were also increased in other tissues. The increased mutation burdens were of multiple mutational signatures characterised by C > A changes. Different mutation rates and signatures between individuals are likely due to different MUTYH mutations or additional inherited mutations in other BER pathway genes. The elevated base substitution rate in normal cells likely accounts for the predisposition to neoplasia in MAP. Despite ubiquitously elevated mutation rates, individuals with MAP do not display overt evidence of premature ageing. Thus, accumulation of somatic mutations may not be sufficient to cause the global organismal functional decline of ageing.
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http://dx.doi.org/10.1038/s41467-022-31341-0 | DOI Listing |
Nat Commun
December 2024
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT, 05405, USA.
8-oxoguanine (8-oxoG) is a common oxidative DNA lesion that causes G > T substitutions. Determinants of local and regional differences in 8-oxoG-induced mutability across genomes are currently unknown. Here, we show DNA oxidation induces G > T substitutions and insertion/deletion (INDEL) mutations in human cells and cancers.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Engelhardt Institute of Molecular Biology, the Russian Academy of Sciences, 119991 Moscow, Russia.
Assessments of breast cancer (BC) risk in carriers of pathogenic variants identified by gene panel testing in different populations are highly in demand worldwide. We performed target sequencing of 78 genes involved in DNA repair in 860 females with BC and 520 age- and family history-matched controls from Central Russia. Among BC patients, 562/860 (65.
View Article and Find Full Text PDFClin Transl Oncol
December 2024
Hereditary Cancer Unit, Medical Oncology Department, Puerta de Hierro University Hospital, Majadahonda, 28222, Madrid, Spain.
Background: APC and MUTYH genes are key in hereditary attenuated adenomatous polyposis syndromes. Guidelines recommend genetic testing based on polyp count, often overlooking age despite its impact on polyp prevalence.
Aim: To enhance genetic testing strategies for suspected attenuated adenomatous polyposis by combining polyp count and age in a probability calculator.
Genet Test Mol Biomarkers
December 2024
Department of Cardiac Surgery, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No. 3333 Binsheng Road, Hangzhou, China.
Tetralogy of Fallot (TOF) is the most common cyanotic heart defect in newborns, with a complex etiology and genetic variation considered to be one of the main pathogenic factors. Identifying genetic variations associated with TOF has important clinical value for understanding its pathogenesis, patient susceptibility, and prognosis of patients with TOF. Therefore, this study aimed to identify potential pathogenic genes of TOF through comprehensive genetic analysis.
View Article and Find Full Text PDFFuture Oncol
December 2024
Division of Oncology, Department of Oncology & Hematology, University Hospital of Modena, Modena, Italy.
Pancreatic Neuroendocrine tumors (pNETs) are a heterogeneous group of neoplasms whose tumor biology is still little known. Thanks to next-generation sequencing, pathogenic mutations in base-excision-repair gene and homologous recombination genes and seem to have a role in the development of pNETs. We assumed that Homologous Recombination Deficiency (HRD) could be a critical pathogenetic mechanism for pNETs.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!