3327461d-c086-4eed-b9f5-eec89b77404f - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001006638 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:63 samples of individuals with ALT-positive neuroblastoma tumors, high coverage whole genome sequencing
| EGAD00001006639 | EGA
Project description:238 samples from individuals with ALT-positive neuroblastoma tumors, high coverage whole genome sequencing
| EGAD00001006626 | EGA
Project description:89 samples of individuals with ALT-positive neuroblastoma tumors, exome sequencing
| EGAD00001006637 | EGA
Project description:144 sample from individuals with ALT-positive neuroblastoma tumors, chip-seq sequencing
| EGAD00001006625 | EGA
Project description:Multi-omics analysis of ALT-positive neuroblastoma tumors
| EGAS00001004349 | EGA
Project description:94 sample with multi-omics analysis of ALT-positive neuroblastoma tumors, rna sequencing
| EGAD00001006587 | EGA
Project description:Telomerase-negative tumors can maintain telomere length by alternative lengthening of telomeres (ALT) but the mechanism of telomere maintenance in ALT cells is not well understood. A significant portion of the relapse Neuroblastoma (NB) tumors are positive for ALT which suggests better dissecting the ALT mechanism could provide novel therapeutic opportunities. TERRA RNA which is derived from the telomere ends is localized to telomeres in R-loop dependent manner and is essential for telomere maintenance. In the present study, we provide evidence that RNA modification at the N6 position of internal adenosine (m6A) in TERRA RNA by methyl transferase METTL3 is essential for telomere maintenance in ALT cells and loss of TERRA m6A/METTL3 leads to accumulation of DNA damage over telomere. Our data suggest that m6A modification in TERRA RNA is required for R-loop formation and telomere targeting of TERRA. We observed that R-loop enriched TERRA is abundantly m6A modified and m6A mediated recruitment of hnRNPA2B1 to TERRA RNA is essential for R-loop formation. Together our study suggests that m6A-mediated R-loop formation could be a widespread mechanism utilized by other chromatin-interacting lncRNAs. We also show treating ALT positive NB cells with small molecule METTL3 inhibitor leads to compromised telomere targeting of TERRA and accumulation of DNA damage over telomere, suggesting METTL3 inhibition could be a therapeutic opportunity for ALT positive NB.
2023-12-13 | GSE219146 | GEO
Project description:Telomerase-negative tumors can maintain telomere length by alternative lengthening of telomeres (ALT) but the mechanism of telomere maintenance in ALT cells is not well understood. A significant portion of the relapse Neuroblastoma (NB) tumors are positive for ALT which suggests better dissecting the ALT mechanism could provide novel therapeutic opportunities. TERRA RNA which is derived from the telomere ends is localized to telomeres in R-loop dependent manner and is essential for telomere maintenance. In the present study, we provide evidence that RNA modification at the N6 position of internal adenosine (m6A) in TERRA RNA by methyl transferase METTL3 is essential for telomere maintenance in ALT cells and loss of TERRA m6A/METTL3 leads to accumulation of DNA damage over telomere. Our data suggest that m6A modification in TERRA RNA is required for R-loop formation and telomere targeting of TERRA. We observed that R-loop enriched TERRA is abundantly m6A modified and m6A mediated recruitment of hnRNPA2B1 to TERRA RNA is essential for R-loop formation. Together our study suggests that m6A-mediated R-loop formation could be a widespread mechanism utilized by other chromatin-interacting lncRNAs. We also show treating ALT positive NB cells with small molecule METTL3 inhibitor leads to compromised telomere targeting of TERRA and accumulation of DNA damage over telomere, suggesting METTL3 inhibition could be a therapeutic opportunity for ALT positive NB.
2023-12-13 | GSE219212 | GEO
Project description:Telomerase-negative tumors can maintain telomere length by alternative lengthening of telomeres (ALT) but the mechanism of telomere maintenance in ALT cells is not well understood. A significant portion of the relapse Neuroblastoma (NB) tumors are positive for ALT which suggests better dissecting the ALT mechanism could provide novel therapeutic opportunities. TERRA RNA which is derived from the telomere ends is localized to telomeres in R-loop dependent manner and is essential for telomere maintenance. In the present study, we provide evidence that RNA modification at the N6 position of internal adenosine (m6A) in TERRA RNA by methyl transferase METTL3 is essential for telomere maintenance in ALT cells and loss of TERRA m6A/METTL3 leads to accumulation of DNA damage over telomere. Our data suggest that m6A modification in TERRA RNA is required for R-loop formation and telomere targeting of TERRA. We observed that R-loop enriched TERRA is abundantly m6A modified and m6A mediated recruitment of hnRNPA2B1 to TERRA RNA is essential for R-loop formation. Together our study suggests that m6A-mediated R-loop formation could be a widespread mechanism utilized by other chromatin-interacting lncRNAs. We also show treating ALT positive NB cells with small molecule METTL3 inhibitor leads to compromised telomere targeting of TERRA and accumulation of DNA damage over telomere, suggesting METTL3 inhibition could be a therapeutic opportunity for ALT positive NB.
2023-12-13 | GSE240690 | GEO
Project description:Telomere attrition ultimately leads to the activation of protective cellular responses such as apoptosis or senescence. Impairment of such mechanisms can allow continued proliferation despite the presence of dysfunctional telomeres. Under such conditions, high levels of genome instability are often engendered. Data from both mouse and human model systems indicate that a period of genome instability might facilitate tumorigenesis. Here, we employ a liposarcoma model system to assay telomere maintenance mechanism-specific genetic alterations. A multiassay approach was used to assess the telomere maintenance mechanism(s) active in tumors. Genomic DNA from these samples was then analyzed by high resolution DNA mapping array in order to identify genetic alterations. Our data reveal a higher level of genome instability in ALT-positive tumors as compared with telomerase-positive tumors, whereas tumors lacking both mechanisms have relatively low levels of genome instability. The bulk of the genetic changes are amplifications, regardless of the mode of telomere maintenance employed. We also identified genetic changes specific to the ALT mechanism, e.g., deletion of chromosome 1q32.2-q44, as well as changes that are underrepresented amongst ALT-positive tumors, such as amplification of chromosome 12q14.3-q21.2. Taken together, these studies provide insight into the molecular pathways involved in the regulation of ALT and reveal several loci that might be exploited either as prognostic markers or targets of chemotherapeutic intervention. Keywords: genotype, genome instability, copy number alteration, liposarcoma, ALT, telomerase, telomere
2008-05-01 | GSE8046 | GEO