Homo sapiens
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PROVIDER: PRJNA132283 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:16 replication error proficient (RER-/MSI-) and 14 replication error deficient (RER+/MSI+) colorectal cancer cell lines Replication error deficient (RER+) colorectal cancers are a distinct subset of colorectal cancers, characterised by inactivation of the DNA mismatch repair system. They are typically pseudodiploid, accumulate mutations in repetitive sequences as a result of their mismatch repair deficiency, and have distinct pathologies. Regulatory sequences controlling all aspects of mRNA processing, including especially message stability are found in the 3âUTR sequence of most genes. The relevant sequences are typically A/U rich elements and/or U repeats. Microarray analysis of 14 RER+ (deficient) and 16 RER- (proficient) colorectal cancer (CRC) cell lines confirms a striking difference in expression profiles. Analysis of the incidence of mononucleotide repeat sequences in the 3âUTRs, 5âUTRs and coding sequences of those genes most differentially expressed in RER+ versus â cell lines has shown that much of this differential expression can be explained by the occurrence of a massive enrichment of genes with 3âUTR T repeats longer than 11 base pairs in the most differentially expressed genes. This enrichment was confirmed by analysis of two published consensus sets of RER differentially expressed probe sets for a large number of primary colorectal cancers. Sequence analysis of the 3âUTRs of a selection of the most differentially expressed genes shows that they all contain deletions in these repeats in all RER+ cell lines studied. These data strongly imply that deregulation of mRNA stability through accumulation of mutations in repetitive regulatory 3âUTR sequences underlies the striking difference in expression profiles between RER+ and RER- colorectal cancers. 16 replication error proficient (RER-/MSI-) and 14 replication error deficient (RER+/MSI+) colorectal cancer cell lines.
2010-10-19 | E-GEOD-24795 | biostudies-arrayexpress
Project description:16 replication error proficient (RER-/MSI-) and 14 replication error deficient (RER+/MSI+) colorectal cancer cell lines Replication error deficient (RER+) colorectal cancers are a distinct subset of colorectal cancers, characterised by inactivation of the DNA mismatch repair system. They are typically pseudodiploid, accumulate mutations in repetitive sequences as a result of their mismatch repair deficiency, and have distinct pathologies. Regulatory sequences controlling all aspects of mRNA processing, including especially message stability are found in the 3’UTR sequence of most genes. The relevant sequences are typically A/U rich elements and/or U repeats. Microarray analysis of 14 RER+ (deficient) and 16 RER- (proficient) colorectal cancer (CRC) cell lines confirms a striking difference in expression profiles. Analysis of the incidence of mononucleotide repeat sequences in the 3’UTRs, 5’UTRs and coding sequences of those genes most differentially expressed in RER+ versus – cell lines has shown that much of this differential expression can be explained by the occurrence of a massive enrichment of genes with 3’UTR T repeats longer than 11 base pairs in the most differentially expressed genes. This enrichment was confirmed by analysis of two published consensus sets of RER differentially expressed probe sets for a large number of primary colorectal cancers. Sequence analysis of the 3’UTRs of a selection of the most differentially expressed genes shows that they all contain deletions in these repeats in all RER+ cell lines studied. These data strongly imply that deregulation of mRNA stability through accumulation of mutations in repetitive regulatory 3’UTR sequences underlies the striking difference in expression profiles between RER+ and RER- colorectal cancers.
2010-10-19 | GSE24795 | GEO
Project description:An enduring issue in evolutionary and cancer biology is how replication infidelity influences genome composition and vice versa. Here we examine this issue by sequencing the genomes of diploid budding yeast strains that are either mismatch repair (MMR) proficient or deficient and encode wild type or mutator variants of the three major nuclear DNA replicases. Analysis of over 43,000 mutations that accumulated in the absence of selective pressure demonstrates that the nuclear DNA replication machinery generates less than one mismatch per genome and in combination with MMR, achieves a genome-wide per base error rate of 1.7 x 10-10. Absent both MMR and purifying selection, replication error patterns strongly depend on replication origin proximity, replication fork direction, and the local DNA sequence. Preferred sequences were observed for base substitutions and deletions. Error rates also vary with replication time, in linker versus nucleosome-bound DNA, in 5'- and 3'-untranslated regions, in coding regions and in intergenic DNA. This genome-wide view shows that replication fidelity is amazingly high but heterogeneous, in patterns that suggest the underlying mechanisms by which replication modulates genome stability and composition and vice versa. Six to ten isolates were sequenced for each combination of DNA polymerase (WT, pol1-L868M, pol2-M644G, pol3-L612M) and mismatch repair (proficient, deficient) genotypes. A single WT isolate was sequenced following micrococcal nuclease digestion.
2014-08-25 | E-GEOD-56939 | biostudies-arrayexpress
Project description:An enduring issue in evolutionary and cancer biology is how replication infidelity influences genome composition and vice versa. Here we examine this issue by sequencing the genomes of diploid budding yeast strains that are either mismatch repair (MMR) proficient or deficient and encode wild type or mutator variants of the three major nuclear DNA replicases. Analysis of over 43,000 mutations that accumulated in the absence of selective pressure demonstrates that the nuclear DNA replication machinery generates less than one mismatch per genome and in combination with MMR, achieves a genome-wide per base error rate of 1.7 x 10-10. Absent both MMR and purifying selection, replication error patterns strongly depend on replication origin proximity, replication fork direction, and the local DNA sequence. Preferred sequences were observed for base substitutions and deletions. Error rates also vary with replication time, in linker versus nucleosome-bound DNA, in 5'- and 3'-untranslated regions, in coding regions and in intergenic DNA. This genome-wide view shows that replication fidelity is amazingly high but heterogeneous, in patterns that suggest the underlying mechanisms by which replication modulates genome stability and composition and vice versa.
2014-08-25 | GSE56939 | GEO
Project description:Lynch syndrome and Familial colorectal cancer type X (FCCTX) are clinically diagnosed using the same criteria, but genomic differences exist between these two groups and the genomic profiles share similarities with their sporadic counterparts, mismatch repair (MMR) deficient and proficient tumors, respectively. Array-based comparative genomic hybridization was performed on 91 tumors, comprising 23 Lynch syndrome (AH), 23 FCCTX (AA), 23 sporadic MMR deficient (AM) and 22 sporadic MMR proficient tumors, in order to identify differences between Lynch syndrome and FCCTX.
2012-06-01 | E-GEOD-38405 | biostudies-arrayexpress
Project description:Lynch syndrome and Familial colorectal cancer type X (FCCTX) are clinically diagnosed using the same criteria, but genomic differences exist between these two groups and the genomic profiles share similarities with their sporadic counterparts, mismatch repair (MMR) deficient and proficient tumors, respectively.
2012-06-02 | GSE38405 | GEO
Project description:Background. Colorectal cancer develops through two main genetic instability pathways characterized by distinct pathologic features and clinical outcome. Results. We investigated colon cancer samples (23 characterized by microsatellite stability, MSS, and 16 by high microsatellite instability, MSI-H) for genome-wide expression of microRNA (miRNA) and mRNA. Based on combined miRNA and mRNA gene expression, a molecular signature consisting of twenty seven differentially expressed genes, inclusive of 8 miRNAs, could correctly distinguish MSI-H versus MSS colon cancer samples. Among the differentially expressed miRNAs, various members of the oncogenic miR-17-92 family were significantly up-regulated in MSS cancers. The majority of protein coding genes were also up-regulated in MSS cancers. Their functional classification revealed that they were most frequently associated with cell cycle, DNA replication, recombination, repair, gastrointestinal disease and immune response. Conclusions. This is the first report that indicates the existence of differences in miRNA expression between MSS versus MSI-H colorectal cancers. In addition, the work suggests that the combination of mRNA/miRNA expression signatures may represent a general approach for improving bio-molecular classification of human cancer.
2007-09-07 | E-TABM-326 | biostudies-arrayexpress
Project description:Alternative polyadenylation (APA) creates distinct transcripts from the same gene by cleaving the pre-mRNA at poly(A) sites that can lie within the 3' UTR, introns, or exons. Most studies focus on APA within the 3' UTR, but here we show that CPSF6 insufficiency alters protein levels and causes a developmental syndrome by deregulating APA throughout the transcript. In neonatal humans and zebrafish larvae, CPSF6 insufficiency shifts poly(A) site usage between the 3'UTR and internal sites in a pathway-specific manner. Genes associated with neuronal function undergo mostly intronic APA, reducing their expression, while genes associated with heart and skeletal function mostly undergo 3' UTR APA and are upregulated. This suggests that, in healthy conditions, cells toggle between internal and 3'UTR APA to modulate protein expression.
2022-11-21 | MSV000090759 | MassIVE
Project description:Lynch syndrome, caused by germline heterozygous mutations of the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2, or deletions affecting the EPCAM gene upstream of MSH2, is characterized by a predisposition to early-onset colorectal and additional extracolonic cancers. An alternative but rare cause of Lynch syndrome is a constitutional epimutation of MLH1, which is characterized by promoter methylation and transcriptional silencing of a single allele in normal tissues. Worldwide, five families with autosomal dominant transmission of a constitutional MLH1 epimutation linked to an MLH1 haplotype with two single nucleotide variants (c.-27C>A and c.85G>T) have been identified. Array-based genotyping using Affymetrix SNP 6.0 data in four of these families revealed a shared haplotype extending across a ≤2.6 Mb region of chromosome 3p22 encompassing MLH1 and additional flanking genes, indicating common ancestry. Genomic DNA from 5 carriers of the c.-27C>A and c.85G>T variants was hybridized on Affymetrix SNP6.0 array according to manufacturer's procedures
2013-04-01 | E-GEOD-45149 | biostudies-arrayexpress
Project description:Chromosomal instable colorectal cancer is marked by specific large chromosomal copy number aberrations. Recently, focal aberrations of 3Mb or smaller have been identified as a common phenomenon in cancer. Inherent to their limited size, these aberrations harbour one or few genes. The aim of this study is to identify recurrent focal chromosomal aberrations and their candidate driver genes in a well defined series of stage II colon cancers and assess their potential clinical relevance. High resolution DNA copy number profiles were obtained from 38 formalin fixed paraffin embedded colon cancer samples with matched normal mucosa as a reference using array comparative genomic hybridization. In total, 81 focal chromosomal aberrations were identified that harboured 177 genes. Statistical validation of focal aberrations and identification of candidate driver genes was performed by enrichment analysis and mapping copy number and mutation data of colorectal-, breast-, pancreatic cancer and glioblastomas to loci of focal aberrations in stage II colon cancer. This analysis demonstrated a significant overlap with previously identified focal amplifications in colorectal cancer, but not with cancers from other sites. In contrast, focal deletions seem less tumour type specific since they also show significant overlap with focal deletions of other sites. Focal deletions detected are significantly enriched for cancer genes and genes frequently mutated in colorectal cancer. The mRNA expression of these genes is significantly correlated with DNA copy number status, supporting the relevance of focal aberrations. Loss of 5q34 and gain of 13q22.1 were identified as independent prognostic factors of survival in this series of patients. In conclusion, focal chromosomal copy number aberrations in stage II colon cancer are enriched in cancer genes which contribute to and drive the process of colorectal cancer development. DNA copy number status of these genes correlate with mRNA expression and some are associated with clinical outcome. 38 Stage II colorectal cancer (CRC) tissue samples (FFPE) of which 19 were done on expression arrays. One sample (Stage II colorectal cancer tissue samples (FFPE) 26) was also done on the 135K NimbleGen array. Fresh frozen and FFPE of the same CRC stage I sample was done on 105K agilent. The fresh frozen was across array in silico set out against a pool of blood of 18 healthy females.
2010-04-19 | E-GEOD-17047 | biostudies-arrayexpress