Genomic factors involved in chromosome rearrangements
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA268998 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Chromosome segregation errors have been linked to DNA damage and genomic rearrangements. Accumulating evidence has shown that catastrophic genomic rearrangements, like chromothripsis, can result from lagging chromosomes undergoing aberrant DNA replication and DNA damage in micronuclei. Detailed characterization of genomic rearrangements resulting from DNA damage in micronuclei has been hampered because of difficulties in culturing daughter cells with DNA damage. Here, we employ a method by which a specific single chromosome is trapped in a micronucleus, followed by transfer to an acceptor cell. Next, stably propagating clonal cell lines with an extra chromosome were established and analyzed by copy number profiling and whole genome sequencing. While non-transformed, p53 proficient and telomerase-immortalized RPE1 cells showed a stable genome following addition of the transferred chromosome, we observed frequent de novo genomic rearrangements in cells derived from the HCT116 colorectal cancer cell line after chromosome transfer. The de novo rearrangements varied from simple deletions and duplications to complex rearrangements. Phase-informative SNPs revealed that the rearrangements specifically occurred on the transferred chromosome. We found that the complex rearrangements recapitulated all features of chromothripsis, including massive oscillation between two copy number states, localization to a single chromosome, random joining of chromosome fragments and non-homologous or micro-homologous repair. We describe an approach that enables the isolation of clonal cell lines with genomic rearrangements and chromothripsis on a specific chromosome in p53 proficient cells. The procedure enables further investigation of the exact mechanism leading to chromothripsis and the analysis of its consequences for cell survival (viability) and cancer development.
2015-08-13 | GSE71978 | GEO
Project description:Chromosome segregation errors have been linked to DNA damage and genomic rearrangements. Accumulating evidence has shown that catastrophic genomic rearrangements, like chromothripsis, can result from lagging chromosomes undergoing aberrant DNA replication and DNA damage in micronuclei. Detailed characterization of genomic rearrangements resulting from DNA damage in micronuclei has been hampered because of difficulties in culturing daughter cells with DNA damage. Here, we employ a method by which a specific single chromosome is trapped in a micronucleus, followed by transfer to an acceptor cell. Next, stably propagating clonal cell lines with an extra chromosome were established and analyzed by copy number profiling and whole genome sequencing. While non-transformed, p53 proficient and telomerase-immortalized RPE1 cells showed a stable genome following addition of the transferred chromosome, we observed frequent de novo genomic rearrangements in cells derived from the HCT116 colorectal cancer cell line after chromosome transfer. The de novo rearrangements varied from simple deletions and duplications to complex rearrangements. Phase-informative SNPs revealed that the rearrangements specifically occurred on the transferred chromosome. We found that the complex rearrangements recapitulated all features of chromothripsis, including massive oscillation between two copy number states, localization to a single chromosome, random joining of chromosome fragments and non-homologous or micro-homologous repair. We describe an approach that enables the isolation of clonal cell lines with genomic rearrangements and chromothripsis on a specific chromosome in p53 proficient cells. The procedure enables further investigation of the exact mechanism leading to chromothripsis and the analysis of its consequences for cell survival (viability) and cancer development.
2015-08-13 | GSE71928 | GEO
Project description:Chromosome segregation errors have been linked to DNA damage and genomic rearrangements. Accumulating evidence has shown that catastrophic genomic rearrangements, like chromothripsis, can result from lagging chromosomes undergoing aberrant DNA replication and DNA damage in micronuclei. Detailed characterization of genomic rearrangements resulting from DNA damage in micronuclei has been hampered because of difficulties in culturing daughter cells with DNA damage. Here, we employ a method by which a specific single chromosome is trapped in a micronucleus, followed by transfer to an acceptor cell. Next, stably propagating clonal cell lines with an extra chromosome were established and analyzed by copy number profiling and whole genome sequencing. While non-transformed, p53 proficient and telomerase-immortalized RPE1 cells showed a stable genome following addition of the transferred chromosome, we observed frequent de novo genomic rearrangements in cells derived from the HCT116 colorectal cancer cell line after chromosome transfer. The de novo rearrangements varied from simple deletions and duplications to complex rearrangements. Phase-informative SNPs revealed that the rearrangements specifically occurred on the transferred chromosome. We found that the complex rearrangements recapitulated all features of chromothripsis, including massive oscillation between two copy number states, localization to a single chromosome, random joining of chromosome fragments and non-homologous or micro-homologous repair. We describe an approach that enables the isolation of clonal cell lines with genomic rearrangements and chromothripsis on a specific chromosome in p53 proficient cells. The procedure enables further investigation of the exact mechanism leading to chromothripsis and the analysis of its consequences for cell survival (viability) and cancer development. We analyzed 38 cell clones, originating from HCT116 or RPE1 cells respectively, with Illumina beadchip arrays to test for unique de novo copy number variants and to determine the chromosome affacted by the CNAs.
2015-08-13 | E-GEOD-71928 | biostudies-arrayexpress
Project description:Chromosome segregation errors have been linked to DNA damage and genomic rearrangements. Accumulating evidence has shown that catastrophic genomic rearrangements, like chromothripsis, can result from lagging chromosomes undergoing aberrant DNA replication and DNA damage in micronuclei. Detailed characterization of genomic rearrangements resulting from DNA damage in micronuclei has been hampered because of difficulties in culturing daughter cells with DNA damage. Here, we employ a method by which a specific single chromosome is trapped in a micronucleus, followed by transfer to an acceptor cell. Next, stably propagating clonal cell lines with an extra chromosome were established and analyzed by copy number profiling and whole genome sequencing. While non-transformed, p53 proficient and telomerase-immortalized RPE1 cells showed a stable genome following addition of the transferred chromosome, we observed frequent de novo genomic rearrangements in cells derived from the HCT116 colorectal cancer cell line after chromosome transfer. The de novo rearrangements varied from simple deletions and duplications to complex rearrangements. Phase-informative SNPs revealed that the rearrangements specifically occurred on the transferred chromosome. We found that the complex rearrangements recapitulated all features of chromothripsis, including massive oscillation between two copy number states, localization to a single chromosome, random joining of chromosome fragments and non-homologous or micro-homologous repair. We describe an approach that enables the isolation of clonal cell lines with genomic rearrangements and chromothripsis on a specific chromosome in p53 proficient cells. The procedure enables further investigation of the exact mechanism leading to chromothripsis and the analysis of its consequences for cell survival (viability) and cancer development. We analyzed 38 cell clones, originating from HCT116 or RPE1 cells respectively, with Illumina beadchip arrays to test for unique de novo copy number variants and to determine the chromosome affacted by the CNAs.
2015-08-13 | E-GEOD-71978 | biostudies-arrayexpress
Project description:Genomic factors involved in chromosome rearrangements
| PRJNA268999 | ENA
Project description:Induced genomic rearrangements and chromothripsis by micronucleus-mediated chromosome transfer
| PRJNA292650 | ENA
Project description:Comparative and population genomic analyses of chromosome rearrangements in Brenthis butterflies
| PRJEB62818 | ENA
Project description:DNA-PKcs Suppresses Illegitimate Chromosome Rearrangements
| PRJNA1049124 | ENA
Project description:Copy number variations and genomic rearrangements in the CFH-CFHRs region were assessed with a custom-designed high-density 8x15k oligonucleotide CGH arrays spanning the RCA gene cluster region in human chromosome 1q32 (median resolution of 110 bp) (AMADID 040193, Agilent Technologies, Santa Clara, CA). A healthy male donor sample, fully genotyped for that region, was used as hybridization control. Microarray data were extracted and visualized using the Feature Extraction Software v10.7 and Genomic Workbench Standard Edition 7.0 (Agilent Corp, Santa Clara, CA). Copy number altered regions were detected using ADM-2 (set as 5) statistic provided by DNA Analytics, with a minimum number of 5 consecutive probes. Genomic build hg19 was used for the experiment.
2013-05-28 | GSE45585 | GEO
Project description:Chromosomal instability (CIN) generates micronuclei, aberrant extranuclear structures that catalyze the acquisition of complex chromosomal rearrangements present in cancer. Micronuclei are characterized by persistent DNA damage and catastrophic nuclear envelope collapse, exposing DNA to the cytoplasm and driving a pro-inflammatory, pro-metastatic environment. Here, we identify the autophagic receptor p62/SQSTM1 as a regulator of micronuclei. p62 modulates micronuclear stability, influencing chromosome fragmentation and rearrangements, via exerting local spatial control on peri-micronuclear ESCRT-mediated repair activity. We demonstrate that proximity of micronuclei to mitochondria leads to oxidation-driven homo-oligomerization of p62, which triggers autophagic degradation of ESCRT components, thereby limiting their repair activity. Notably, we find that p62 levels correlate with increased chromothripsis across human cancer cell lines and with increased CIN in colorectal tumors. Thus, our study identifies p62 as a novel regulator of micronuclei and indicates that it may serve as a prognostic marker of tumors with high CIN.
2024-09-02 | PXD052675 | Pride