The genomic landscape of colitis-associated colorectal carcinomas is dominated by TP53 mutations, aneuploidy and gains of chromosome arm 5p
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE156076 | GEO | 2022/02/01
REPOSITORIES: GEO
Similar Datasets
Project description:The genomic landscape of colitis-associated colorectal carcinomas is dominated by TP53 mutations, aneuploidy and gains of chromosome arm 5p
| PRJNA656709 | ENA
Project description:Aneuploidy promotes genomic instability by impairing DNA replication
| PRJEB7596 | ENA
Project description:Aneuploidy causes a proliferative disadvantage in all normal cells analyzed to date, yet this condition is associated with a disease characterized by unabated proliferative potential, cancer. The mechanisms that allow cancer cells to tolerate the adverse effects of aneuploidy are not known. To probe this question, we identified aneuploid yeast strains with improved proliferative abilities. Their molecular characterization revealed strain-specific genetic alterations as well as mutations shared between different aneuploid strains. Among the latter, a loss-of-function mutation in the gene encoding the deubiquitinating enzyme Ubp6 improves growth rates in four different aneuploid yeast strains by attenuating the changes in intracellular protein composition caused by aneuploidy. Our results demonstrate the existence of aneuploidy-tolerating mutations that improve the fitness of multiple different aneuploidies and highlight the importance of ubiquitin-proteasomal degradation in suppressing the adverse effects of aneuploidy.
2010-02-25 | GSE20464 | GEO
Project description:There are many different types and origins of aneuploidy, but whether there is a uniform cellular response to aneuploidy in human cells has not been addressed so far. To uncover a uniform transcriptional response to aneuploidy we evaluted the transcription profiles of trisomic and tetrasomic cell lines and cell lines with complex aneuploid karyotypes.
2014-02-19 | GSE47830 | GEO
Project description:Aneuploidy causes a proliferative disadvantage in all cells analyzed to date, yet this condition is associated with a disease characterized by unabated proliferative potential, cancer. The mechanisms that allow cancer cells to tolerate the adverse effects of aneuploidy are not known. To probe this question, we identified aneuploid yeast strains with high proliferative abilities and characterized their genetic alterations. We found both strain-specific genetic alterations and mutations shared between different aneuploid strains. One such mutation, a loss of function mutation in the gene encoding the deubiquitinating enzyme UBP6, improves growth rates in four different aneuploid yeast strains. Our data further suggest that deletion of UBP6 attenuates the effects of aneuploidy on cellular protein composition. Our results demonstrate the existence of aneuploidy-tolerating mutations that improve the fitness of multiple different aneuploidies and highlight the importance of ubiquitin-proteasomal degradation in suppressing the adverse effects of aneuploidy. This dataset contains both expression analysis and CGH of yeast strains bearing extra chromosomes. In all cases, the wt euploid strain grown under the same conditions was used as the reference sample. Reference nucleic acid was generally labeled with Cy3, though some were labeled with Cy5 as indicated in the associated annotations for each array. No replicate arrays are included. Expression Samples: GSM513249-GSM513277 CGH Samples: GSM513278-GSM513369
2010-02-24 | E-GEOD-20464 | biostudies-arrayexpress
Project description:Aneuploidy causes severe developmental defects and is a near universal feature of tumor cells. Despite its profound effects, the cellular processes affected by aneuploidy are not well characterized. Here, we examined the consequences of aneuploidy on the proteome of aneuploid budding yeast strains. We show that although protein levels largely scale with gene copy number, subunits of multi-protein complexes are notable exceptions. Posttranslational mechanisms attenuate their expression when their encoding genes are in excess. Our proteomic analyses further revealed a novel aneuploidy-associated protein expression signature characteristic of altered metabolism and redox homeostasis. Indeed aneuploid cells harbor increased levels of reactive oxygen species (ROS). Interestingly, increased protein turnover attenuates ROS levels and this novel aneuploidy-associated signature and improves the fitness of most aneuploid strains. Our results show that aneuploidy causes alterations in metabolism and redox homeostasis. Cells respond to these alterations through both transcriptional and posttranscriptional mechanisms.
2014-08-14 | PXD001019 | Pride
Project description:An unbalanced karyotype, a condition known as aneuploidy, has a profound impact on cellular physiology and is a hallmark of cancer. Determining how aneuploidy affects cells is thus critical to understanding tumorigenesis. Here we show that aneuploidy interferes with the degradation of autophagosomes within lysosomes. Mis-folded proteins that accumulate in aneuploid cells due to aneuploidy-induced proteomic changes overwhelm the lysosome with cargo, leading to the observed lysosomal degradation defects. Importantly, aneuploid cells respond to lysosomal saturation. They activate a lysosomal stress pathway that specifically increases the expression of genes needed for autophagy-mediated protein degradation. Our results reveal lysosomal saturation as a universal feature of the aneuploid state that must be overcome during tumorigenesis.
2015-10-26 | GSE60570 | GEO
Project description:Aneuploidy, or an aberrant karyotype, results in developmental disabilities and has been implicated in tumorigenesis. However, the causes of aneuploidy-induced phenotypes and the consequences of aneuploidy on cell physiology remain poorly understood. We have performed a meta-analysis on gene expression data from aneuploid cells in diverse organisms, including yeast, plants, mice, and humans. We found highly-related gene expression patterns that are conserved between species: genes that were involved in the response to stress were consistently upregulated, while genes associated with the cell cycle and cell proliferation were downregulated in aneuploid cells. Within species, different aneuploidies induced similar changes in gene expression, independent of the specific chromosomal aberrations. Taken together, our results demonstrate that aneuploidies of different chromosomes and in different organisms impact similar cellular pathways and cause a stereotypical anti-proliferative response that must be overcome prior to transformation.
2012-06-29 | GSE35853 | GEO