Proteogenomic analysis reveals adaptive strategies for alleviating the consequences of aneuploidy in cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1072666 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Aneuploidy is prevalent in cancer, conferring fitness advantage, multidrug resistance, and poor prognosis. In contrast, experimentally induced aneuploidy often results in adverse effects and impaired proliferation. This paradox underscores the necessity of cancer cells to adapt to abnormal chromosome numbers. To identify molecular mechanisms of adaptation to aneuploidy, we initiated in vitro evolution of cells with extra chromosomes added via microcell-mediated chromosome transfer. To this end, we cultured cells in a nutrient-rich medium for 50 passages or plated the cells at a low density and selectively collected the largest colonies originating from a single cell (colony selection). The anaylsis of somatic copy number variations in the evolved cell lines was then carried out based on low-coverage whole genome sequencing (WGS) and array-based comparative genomic hybridization (aCGH).
2024-03-04 | GSE254936 | 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. These experiments are two-color hybridizations of RNA isolated from aneuploid samples vs matched wt cells, all grown to midlog phase.
2012-06-28 | E-GEOD-35853 | biostudies-arrayexpress
Project description:Aneuploidy is prevalent in cancer, conferring fitness advantage, multidrug resistance, and poor prognosis. In contrast, experimentally induced aneuploidy often results in adverse effects and impaired proliferation. This paradox underscores the necessity of cancer cells to adapt to abnormal chromosome numbers. To identify molecular mechanisms of adaptation to aneuploidy, we initiated in vitro evolution of cells with extra chromosomes added via microcell-mediated chromosome transfer. To this end, we cultured cells in a nutrient-rich medium for 50 passages or plated the cells at a low density and selectively collected the largest colonies originating from a single cell (colony selection). The anaylsis global proteoms of the evolved cell lines was then carried out using TMT quantification strategy. This dataset also includes measurements from post-xenograft aneuploid cell line.
2025-01-14 | PXD049120 | Pride
Project description:Aneuploidy is prevalent in cancer, conferring fitness advantage, multidrug resistance, and poor prognosis. In contrast, experimentally induced aneuploidy often results in adverse effects and impaired proliferation. This paradox underscores the necessity of cancer cells to adapt to abnormal chromosome numbers. To identify molecular mechanisms of adaptation to aneuploidy, we initiated in vitro evolution of cells with extra chromosomes added via microcell-mediated chromosome transfer. To this end, we cultured cells in a nutrient-rich medium for 50 passages or plated the cells at a low density and selectively collected the largest colonies originating from a single cell (colony selection). The anaylsis of global proteomes of the evolved cell lines was then carried out using a TMT quantification strategy. This data set also includes data from trisomic cells with and without TP53 k.o.
2025-01-14 | PXD049124 | Pride
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
Project description:Aneuploidy is prevalent in cancer, conferring fitness advantage, multidrug resistance, and poor prognosis. In contrast, experimentally induced aneuploidy often results in adverse effects and impaired proliferation. This paradox underscores the necessity of cancer cells to adapt to abnormal chromosome numbers. To identify molecular mechanisms of adaptation to aneuploidy, we initiated in vitro evolution of cells with extra chromosomes added via microcell-mediated chromosome transfer. To this end, we cultured cells in a nutrient-rich medium for 50 passages or plated the cells at a low density and selectively collected the largest colonies originating from a single cell (colony selection). One of the striking observations following evolution of cells with extra chromosome 5 in HCT116 cell line was the frequent loss of the 5q, while maintaining the 5p arm after in vitro evolution. Chromosome 5 is a frequent target of large copy number alterations in several malignancies, such as ovarian, gastric, and oesophageal cancer, and malignant myeloid diseases. Moreover, analysis of chromosome arm level events in the TCGA dataset clearly shows that loss of chromosome arm 5q and gain of 5p are among the most frequent events. We asked whether these specific changes in copy numbers of chromosome 5 – loss of 5q with simultaneous retention of 5p – could affect the proliferation of the evolved cells. To this end, we used the recently developed technique ReDACT-TR (Restoring Disomy in Aneuploid cells using CRISPR Targeting with Telomere Replacement (Girish et al., 2023)), and transfected cells of a separate clone of Htr5 (before evolution) with a gRNA that cuts near the centromere of chromosome 5, simultaneously with a cassette encoding ~100 repeats of the human telomere seed sequence. Targeting the q-arm generated two independent cell lines with 5p trisomy (Htr5p_1 and Htr5p_2), which were confirmed by FISH with probes specific for 5p and 5q arms and by shallow WGS. No cell lines with trisomy of the q-arm were generated, but we have obtained two diploid cell lines (Hdi5_1 and Hdi5_2), most likely due to the CRISPR/Cas9 induced loss of chromosome 5 (Papathanasiou, Markoulaki et al., 2021, Tsuchida, Brandes et al., 2023). The anaylsis of global proteomes of the ReDACT cell lines was then carried out using a TMT quantification strategy.
2025-01-14 | PXD056432 | Pride
Project description:Consequences of aneuploidy in human fibroblasts with trisomy 21
| PRJNA646219 | ENA
Project description:To characterize aneuploidy driven phenotypes in human trisomies, we performed global transcriptome, proteome, and phenotypic analysis of primary human fibroblasts from individuals with Patau (trisomy 13), Edwards (trisomy 18), or Down syndromes.
2020-07-09 | MSV000085706 | MassIVE
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