EGAS00001004066-sc-2021-08-19T10:20:00Z - samples
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ABSTRACT:
PROVIDER: EGAD00001007997 | EGA |
REPOSITORIES: EGA
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Project description: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 sequenced normal cell DNAs from 10 individuals with MAP and study the somatic mutation burden and mutational signatures.
| EGAD00001007958 | EGA
Project description:Progression of duodenal polyposis into cancer is an important cause of morbidity and mortality in the inherited tumour syndromes Familial Adenomatous Polyposis (FAP) and MUTYH-associated Polyposis (MAP), yet this process remains poorly understood. This study aimed to identify genes that are mutated in FAP and MAP duodenal adenomas and to characterise the cellular consequences for duodenal tumorigenesis.
2023-08-07 | GSE189035 | GEO
Project description:Studying whether removal of base-excision repair from mitochondria will result into increase in mitochondrial DNA (mtDNA) mutation load. The endogenous genes of OGG1 and MUTYH DNA glycosylases were modified to lack the genomic region encoding for the predicted mitochondrial targeting sequence. The mouse lines used: A mouse line that lacks the region encoding for the mitochondrial targeting sequence (L2 to W23) of OGG1 (Ogg1 dMTS mice). A mouse line that lacks the region encoding the mitochondrial targeting sequence (K2 to P33) of MUTYH (Mutyh dMTS mice). To accumulate mutations to the mitochondrial DNA these mice were bred double homozygous Mutyh dMTS x Ogg1 dMTS mice as a maternal lineage for five consecutive generations and mitochondrial DNA from liver was extracted from the offspring and sequenced with Illumina. OGG1 and MUTYH are involved in repair of 8-oxo-dG from DNA. 8-oxo-dG can be a mutagenic lesion because some DNA repair polymerases are known to erroneously incorporate adenosine opposite to 8-oxo-dG during replication leading to GC>TA transversion mutations.
2018-07-13 | E-MTAB-6532 | biostudies-arrayexpress
Project description:Familial adenomatous polyposis (FAP) and MUTYH‐associated polyposis (MAP) are inherited disorders associated with multiple colorectal adenomas that lead to a very high risk of colorectal cancer. The somatic mutations that drive adenoma development in these conditions have not been investigated comprehensively. In this study we performed analysis of paired colorectal adenoma and normal tissue DNA from individuals with FAP or MAP, sequencing 14 adenoma whole exomes (eight MAP, six FAP), 55 adenoma targeted exomes (33 MAP, 22 FAP) and germline DNA from each patient.
| EGAD00001004332 | EGA
Project description:Whole-exome sequencing (WES) and whole-genome sequencing (WGS) were performed on matched adjacent normal tissues, multiregionally sampled adenomas at different stages and carcinomas from 5 patients with FAP and 1 patient with MUTYH-associated polyposis (MAP) (n=56 exomes; n=56 genomes; n=8,757 single cells).
| EGAD00001005457 | EGA
Project description:Data from Excision-seq experiments to map deoxyuridine and pyrimidine dimers in S. cerevisiae and E. coli For uracil mapping in pre-digestion Excision-seq, uracil was excised from genomic DNA from dut ung yeast and bacteria yielding double-stranded DNA fragments. Adapters were ligated to these fragments for Illumina library preparation. Using this method, the number of reads at a genomic location corresponds to the quantity of dU at that location. In post-digestion Excision-seq, uracil-containing library fragments are destroyed by UDG treatment, thus coverage is inversely proportional to uracil content. For pyrimidine dimer Excision-seq, yeast were irradiated with high doses of UVC light to generate a large number of DNA modifications. Using the excision repair enzyme UVDE from S. pombe, we excised pyrimidine dimers, cutting the phosphodieseter bond to release small double stranded fragments. These fragments were repaired with either CPD photolyase or 6-4 photolyase to generate independent libraries for each modification type. Illumina adapters were ligated to these fragments for library preparation. Using this method the number of reads at a genomic location corresponds to the quantity of the 3' pyrimidine of the dimer.
2014-05-15 | E-GEOD-51361 | biostudies-arrayexpress
Project description:Expression profiling is a well established tool for the genome-wide analysis of the transcriptional activity of human neoplasia. However, the high sensitivity of this approach combined with the well-known cellular and molecular heterogeneity of cancer often result in extremely complex and extended expression signatures of difficult functional interpretation. The majority of sporadic colorectal cancer cases are triggered by mutations in the APC tumor suppressor gene leading to constitutive activation of the Wnt/b-catenin signaling pathway and adenoma formation. Notwithstanding this common genetic basis, colorectal cancers are very heterogeneous in their degree of differentiation, growth rate and malignant potential. Here, we applied cross-species comparison of expression profiles of intestinal polyps derived from hereditary colorectal cancer patients carrying APC germline mutations, and from a mouse model carrying a targeted inactivating mutation in the mouse homologue Apc. This comparative approach resulted in the establishment of a conserved signature encompassing 166 genes differentially expressed between adenomas and normal intestinal mucosa in both species. Functional analysis of the conserved genes revealed a general increase in cell proliferation and the activation of the Wnt/b-catenin signal transduction pathway, as expected from the selection of APC/Apc-mutant intestinal adenomas. Moreover, the conserved signature is able to resolve expression profiles from hereditary polyposis patients carrying APC germline mutations from those with bi-allelic incativation of the MYH gene. Keywords: normal versus tumor comparison; compare expression profiles from microdissected samples with distinct germline mutations (FAP vs. MAP). Here, we report the expression profiles from normal and intestinal adenomatous tissue from FAP (familial adenomatous polyposis) and MAP (MUTY-associated polyposis) patients with established APC and MUTY germline mutations. Total RNA samples were obtianed by laser capture microdissection.
2008-04-01 | E-GEOD-9689 | biostudies-arrayexpress
Project description:Oxidative DNA damage has been associated with cognitive decline. The Ogg1 and Mutyh DNA glycosylases cooperate to prevent mutations caused by 8-oxoG, a major premutagenic oxidative DNA base lesion. Here, we have examined behavior and cognitive function in mice deficient of these glycosylases. We found that Ogg1-/-Mutyh-/- mice were more active and less anxious and that their learning ability was impaired. In contrast, Mutyh-/- mice showed moderately improved memory compared to WT. There was no change in genomic 8-oxoG levels, suggesting that Ogg1 and Mutyh play minor roles in global repair in adult brain. Notably, transcriptome analysis of hippocampus revealed that differentially expressed genes in the mutant mice belong to pathways known to be involved in anxiety and cognitive function. Thus, beyond their involvement in DNA repair, Ogg1 and Mutyh modulate cognitive function and behavior, and related hippocampal gene expression, suggesting a novel role for 8-oxoG in regulating adaptive behavior.
2015-12-20 | GSE73029 | GEO
Project description:Details of the series are available in the publication Cardoso J. et al., “Chromosomal instability in MYH- and APC-mutant adenomatous polyps”, Cancer Research, accepted for publication. Abstract of the publication: “The vast majority of colorectal cancers display genetic instability, either in the chromosomal (CIN) or microsatellite (MIN) forms. While CIN tumors are per definition aneuploid, MIN colorectal cancers, caused by loss of mismatch repair function, are usually near-diploid. Recently, bi-allelic germline mutations in the MYH gene, were found to be responsible for MAP (MYH associated polyposis), an autosomal recessive predisposition to multiple colorectal polyps, often indistinguishable from the dominant FAP (familial adenomatous polyposis) syndrome caused by inherited APC mutations. Here, we analyzed MYH- and APC-mutant polyps by combining laser-capture microdissection, isothermal genomic DNA amplification, and array-CGH (comparative genomic hybridization). Smoothed quantile regression methods were applied to the MAP and FAP genomic profiles to discriminate chromosomes predominantly affected by gains and losses. Up to 80% of the MAP polyps showed aneuploid changes, which is significantly higher than the 60% found among FAP polyps. Both MAP and FAP adenomas were characterized by frequent losses at chromosome 1p, 17, 19 and 22, and gains affecting chromosome 7 and 13. The observation that aneuploidy is already detectable at early stages of MYH-driven tumorigenesis raises the possibility that CIN may contribute significantly to accelerated tumor progression, increased cancer risk, and poor prognosis in MAP.” Keywords: repeat, BAC, CGH
2005-12-25 | GSE3898 | GEO
Project description:HNF-1β mutations are one of the most common single-gene mutations that underlie kidney developmental disease. Hepatocyte nuclear factor 1β (HNF-1β) is essential for kidney development, but its functions in kidney development are incompletely understood. We identified 8284 HNF-1β binding sites using ChIP-sequencing. The majority of these peaks map to promoter (26%), intron (34%) or distal intergenic regions (37.4%) of the mouse genome. 61% of peaks map to protein coding genes, 12% map to long-noncoding RNAs, and 2% map to miRNAs.
2022-10-20 | GSE205189 | GEO