EGAS00001001343-sc-20170427 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001003307 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:In this project we will use exome sequencing to identify somatic mutations in lesions from a patient with a germline mutation in the protection of telomeres 1 gene (POT1). This dataset contains all the data available for this study on 2016-04-20.
| EGAD00001002050 | EGA
Project description:In this project we will use exome sequencing to identify somatic mutations in lesions from a patient with a germline mutation in the protection of telomeres 1 gene (POT1).
| EGAS00001001343 | EGA
Project description:Telomere protection 1 (POT1) is an important subunit in the shelterin complex, considered the telomere protector. POT1 dysfunction may lead to telomere length dysregulation and genomic instability. Both germline and somatic POT1 mutations have been identified in CLL patients, suggesting the development of the disease. This study aimedto evaluate the occurrence of POT1 mutations throughout CLL's progression and determine their prognostic significance.
2025-03-14 | GSE261569 | GEO
Project description:Pathogenic germline variants in the protection of telomeres 1 gene (POT1) have been associated with predisposition to a range of tumor types, including melanoma, glioma, leukemia and cardioangiosarcoma. We sequenced all coding exons of the POT1 gene in 2,929 European-descent melanoma cases and 3,298 controls, identifying 43 protein-changing genetic variants. We performed functional studies on each of these variants and explored their possible contribution to disease risk.
| EGAD00001009848 | EGA
Project description:Pathogenic germline variants in the protection of telomeres 1 gene (POT1) have been associated with predisposition to a range of tumor types, including melanoma, glioma, leukemia and cardioangiosarcoma. We sequenced all coding exons of the POT1 gene in 2,929 European-descent melanoma cases and 3,298 controls, identifying 43 protein-changing genetic variants. We performed functional studies on each of these variants and explored their possible contribution to disease risk.
| EGAS00001006870 | EGA
Project description:The evolutionarily conserved POT1 protein binds the single stranded G-rich telomeric DNA and has been implicated in telomeric DNA maintenance and the suppression of DNA damage checkpoint signaling. Here, we explore human POT1 function through genetics and proteomics discovering that the complete absence of POT1 leads to severe telomere maintenance defects that had not been anticipated from previous depletion studies. We determine the telomeric proteome upon POT1-loss by implementing an improved telomeric chromatin isolation protocol. Using quantitative proteomics by tandem mass tags (TMT) we identified a large set of proteins involved in nucleic acid metabolism that engage with telomeres upon loss of POT1. Inactivation of the homology directed repair machinery suppresses POT1-loss mediated telomeric DNA defects. Our results unravel as major function of human POT1 the suppression of telomere instability induced by homology directed repair.
2020-10-21 | PXD016826 | Pride
Project description:The conserved Rap1 protein is part of the shelterin complex that plays critical roles in chromosome end protection and telomere length homeostasis. Previous studies addressed how fission yeast Rap1 contributes to telomere length maintenance, but the mechanism by which the protein inhibits end fusions has remained elusive. Here, we use a genetic screen in combination with high throughput sequencing to identify several amino acid positions in Rap1 that have a key role in end protection. Interestingly, mutations at these sites render cells susceptible to genome instability in a conditional manner with longer telomeres being prone to undergoing end fusions, while short telomeres are sufficiently protected. The protection of long telomeres requires their nuclear envelope attachment mediated by the Rap1-Bqt4 interaction. Our data demonstrates that longer telomeres pose an additional challenge for the maintenance of genome integrity and provides an explanation for a species-specific upper limit in telomere length.
2022-08-10 | GSE190759 | GEO
Project description:Germline and somatic alterations in DICER1 and DGCR8 microprocessors confer risk of developing benign and malignant thyroid lesions, yet the molecular events driving malignant transformation remain unclear. We trace the molecular trajectories from benignity to malignancy in DICER1/DGCR8-mutated thyroid lesions using multi-omic profiling on 27 DICER1/DGCR8-mutated samples. Our findings reveal a progressive, specific, and linear accumulation of genetic alterations, which when combined with enhanced downregulation of miRNAs distinguished DICER1/DGCR8-malignant lesions from their benign counterparts. Compensatory hypomethylation of miRNA encoding genes characterised DICER1/DGCR8-benign lesions, but as the tumors progressed to malignancy, methylation was partly reimposed, reversing the attempts to activate miRNA-encoded genes and further compromising miRNA production. Transcriptomic analyses revealed mutation-specific effects on the microenvironment, whereby DICER1 mutations activated canonical thyroid cancer progression pathways, whereas altered DGCR8 associated with immune-related alterations. This work unveils specific molecular events underlying malignant progression of miRNA-biogenesis related thyroid tumors and identifies potential biomarkers and disease etiology mechanisms.
2025-12-10 | GSE300956 | GEO
Project description:Germline and somatic alterations in DICER1 and DGCR8 microprocessors confer risk of developing benign and malignant thyroid lesions, yet the molecular events driving malignant transformation remain unclear. We trace the molecular trajectories from benignity to malignancy in DICER1/DGCR8-mutated thyroid lesions using multi-omic profiling on 27 DICER1/DGCR8-mutated samples. Our findings reveal a progressive, specific, and linear accumulation of genetic alterations, which when combined with enhanced downregulation of miRNAs distinguished DICER1/DGCR8-malignant lesions from their benign counterparts. Compensatory hypomethylation of miRNA encoding genes characterised DICER1/DGCR8-benign lesions, but as the tumors progressed to malignancy, methylation was partly reimposed, reversing the attempts to activate miRNA-encoded genes and further compromising miRNA production. Transcriptomic analyses revealed mutation-specific effects on the microenvironment, whereby DICER1 mutations activated canonical thyroid cancer progression pathways, whereas altered DGCR8 associated with immune-related alterations. This work unveils specific molecular events underlying malignant progression of miRNA-biogenesis related thyroid tumors and identifies potential biomarkers and disease etiology mechanisms.
2025-12-10 | GSE301150 | GEO
Project description:Germline and somatic alterations in DICER1 and DGCR8 microprocessors confer risk of developing benign and malignant thyroid lesions, yet the molecular events driving malignant transformation remain unclear. We trace the molecular trajectories from benignity to malignancy in DICER1/DGCR8-mutated thyroid lesions using multi-omic profiling on 27 DICER1/DGCR8-mutated samples. Our findings reveal a progressive, specific, and linear accumulation of genetic alterations, which when combined with enhanced downregulation of miRNAs distinguished DICER1/DGCR8-malignant lesions from their benign counterparts. Compensatory hypomethylation of miRNA encoding genes characterised DICER1/DGCR8-benign lesions, but as the tumors progressed to malignancy, methylation was partly reimposed, reversing the attempts to activate miRNA-encoded genes and further compromising miRNA production. Transcriptomic analyses revealed mutation-specific effects on the microenvironment, whereby DICER1 mutations activated canonical thyroid cancer progression pathways, whereas altered DGCR8 associated with immune-related alterations. This work unveils specific molecular events underlying malignant progression of miRNA-biogenesis related thyroid tumors and identifies potential biomarkers and disease etiology mechanisms.
2025-12-10 | GSE301163 | GEO