Ontology highlight
ABSTRACT:
PROVIDER: PRJNA678822 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13071000.fastq.gz | Fastqsanger.gz | |||
| SRR13071000_1.fastq.gz | Fastqsanger.gz | |||
| SRR13071000_2.fastq.gz | Fastqsanger.gz | |||
| SRR13071001.fastq.gz | Fastqsanger.gz | |||
| SRR13071001_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 96 |
Similar Datasets
Project description:Transient genomic instability drives tumorigenesis through accelerated clonal evolution
| PRJNA679266 | ENA
Project description:Repetitive sequences are hotspots of evolution at multiple levels. However, due to technical difficulties involved in their assembly and analysis, the role of repeats in tumor evolution is poorly understood. We developed a rigorous motif-based methodology to quantify variations in the repeat content of proteomes and genomes, directly from proteomic and genomic raw sequence data, and applied it to analyze a wide range of tumors and normal tissues. We identify high similarity between the repeat-instability in tumors and their patient-matched normal tissues, but also tumor-specific signatures, both in protein expression and in the genome, that strongly correlate with cancer progression and robustly predict the tumorigenic state. In a patient, the hierarchy of genomic repeat instability signatures accurately reconstructs tumor evolution, with primary tumors differentiated from metastases. We find an inverse relationship between repeat-instability and point mutation load, within and across patients, and independently of other somatic aberrations. Thus, repeat-instability is a distinct, transient and compensatory adaptive mechanism in tumor evolution.
2020-06-02 | PXD012574 | Pride
Project description:Telomere dysfunction drives chromosomal instability (CIN) during the transition from benign adenoma to malignant adenocarcinoma. While CIN provides a mutator mechanism for cancer- relevant genomic events, its role in shaping tumor biology during carcinogenesis is not well understood. Here, we explored the molecular and biological impact of telomere dysfunction and associated CIN in vivo in a faithful model of CRC. In vivo lineage tracing revealed that CIN increased the rate of neoplastic cell clonal expansion through accelerated differentiation of neighboring stem cells, resulting in increased number of adenomas and decreased survival in CIN-high Apcmin mice. Mechanistically, CIN represses EZH2 leading to upregulation of secreted Wnt antagonists, which resulted in a growth advantage to CIN-high neoplastic cells. Correspondingly, pharmacological activation of intrinsic WNT signaling enhanced intestinal stem cells fitness, leading to reduced neoplastic cell clonal expansion and adenoma burden. Thus, the CIN-EZH2-WNT axis enhances intestinal cancer initiation in the nascent tumor microenvironment, providing a preventive strategy for patients harboring germline APC mutations.
2024-03-01 | GSE234030 | GEO
Project description:Telomere dysfunction drives chromosomal instability (CIN) during the transition from benign adenoma to malignant adenocarcinoma. While CIN provides a mutator mechanism for cancer- relevant genomic events, its role in shaping tumor biology during carcinogenesis is not well understood. Here, we explored the molecular and biological impact of telomere dysfunction and associated CIN in vivo in a faithful model of CRC. In vivo lineage tracing revealed that CIN increased the rate of neoplastic cell clonal expansion through accelerated differentiation of neighboring stem cells, resulting in increased number of adenomas and decreased survival in CIN-high Apcmin mice. Mechanistically, CIN represses EZH2 leading to upregulation of secreted Wnt antagonists, which resulted in a growth advantage to CIN-high neoplastic cells. Correspondingly, pharmacological activation of intrinsic WNT signaling enhanced intestinal stem cells fitness, leading to reduced neoplastic cell clonal expansion and adenoma burden. Thus, the CIN-EZH2-WNT axis enhances intestinal cancer initiation in the nascent tumor microenvironment, providing a preventive strategy for patients harboring germline APC mutations.
2024-03-05 | GSE229828 | GEO
Project description:Telomere dysfunction drives chromosomal instability (CIN) during the transition from benign adenoma to malignant adenocarcinoma. While CIN provides a mutator mechanism for cancer- relevant genomic events, its role in shaping tumor biology during carcinogenesis is not well understood. Here, we explored the molecular and biological impact of telomere dysfunction and associated CIN in vivo in a faithful model of CRC. In vivo lineage tracing revealed that CIN increased the rate of neoplastic cell clonal expansion through accelerated differentiation of neighboring stem cells, resulting in increased number of adenomas and decreased survival in CIN-high Apcmin mice. Mechanistically, CIN represses EZH2 leading to upregulation of secreted Wnt antagonists, which resulted in a growth advantage to CIN-high neoplastic cells. Correspondingly, pharmacological activation of intrinsic WNT signaling enhanced intestinal stem cells fitness, leading to reduced neoplastic cell clonal expansion and adenoma burden. Thus, the CIN-EZH2-WNT axis enhances intestinal cancer initiation in the nascent tumor microenvironment, providing a preventive strategy for patients harboring germline APC mutations.
2024-03-01 | GSE234032 | GEO
Project description:Telomere dysfunction drives chromosomal instability (CIN) during the transition from benign adenoma to malignant adenocarcinoma. While CIN provides a mutator mechanism for cancer- relevant genomic events, its role in shaping tumor biology during carcinogenesis is not well understood. Here, we explored the molecular and biological impact of telomere dysfunction and associated CIN in vivo in a faithful model of CRC. In vivo lineage tracing revealed that CIN increased the rate of neoplastic cell clonal expansion through accelerated differentiation of neighboring stem cells, resulting in increased number of adenomas and decreased survival in CIN-high Apcmin mice. Mechanistically, CIN represses EZH2 leading to upregulation of secreted Wnt antagonists, which resulted in a growth advantage to CIN-high neoplastic cells. Correspondingly, pharmacological activation of intrinsic WNT signaling enhanced intestinal stem cells fitness, leading to reduced neoplastic cell clonal expansion and adenoma burden. Thus, the CIN-EZH2-WNT axis enhances intestinal cancer initiation in the nascent tumor microenvironment, providing a preventive strategy for patients harboring germline APC mutations.
2024-03-01 | GSE234031 | GEO
Project description:Topoisomerase 1 dependent R-loop deficiency drives accelerated replication and genomic instability
| PRJNA713795 | ENA
Project description:LINE-1/L1 retrotransposon sequences compose 17% of the human genome. Among the many classes of mobile genetic elements, L1 is the only autonomous retrotransposon that still drives human genomic plasticity today. Through its co-evolution with the human genome, L1 has intertwined itself with host cell biology to aid its proliferation.
2017-05-30 | MSV000081124 | MassIVE
Project description:Intratumor heterogeneity is a major challenge in cancer treatment. To decipher patterns of chromosomal heterogeneity, we analyzed six colorectal cancer cell lines by multiplex interphase FISH. The mismatch repair deficient cell lines DLD-1 and HCT116 had the most stable copy numbers, whereas aneuploid cell lines displayed a higher degree of instability. We subsequently assessed the clonal evolution of a single cell in two aneuploid cell lines, SW480 and HT-29, which both have near-triploid karyotypes but different degrees of chromosomal instability. The clonal compositions of the single cell-derived daughter cell lines, as assessed by multiplex FISH, differed for HT-29 and SW480. Daughters of HT-29 were stable, clonal, and had little heterogeneity. Daughters of SW480 were more heterogeneous, with the single cell-derived daughter cell lines separating into two distinct populations with different ploidy (hyper-diploid and near-triploid), morphology, gene expression and tumorigenicity. To better understand the evolutionary trajectory for the two SW480 populations, we constructed phylogenetic trees which showed ongoing instability in the daughter cell lines.. When analyzing the evolutionary development over time, most single cell-derived daughter cell lines maintained their major clonal pattern, with the exception of one daughter of SW480 that showed a switch involving a loss of APC. Our meticulous analysis of the clonal evolution and composition of these colorectal cancer models shows that all chromosomes are subject to segregation errors, however, specific net genomic imbalances are maintained. Karyotype evolution is driven by the necessity to arrive at and maintain a specific plateau of chromosomal copy numbers as the drivers of carcinogenesis.
2018-05-01 | GSE102647 | GEO
Project description:Cancer cells exhibit rewired transcriptional regulatory networks that promote tumor growth and survival. However, the processes that configure these pathological networks remain poorly understood. Through a pan-cancer epigenomic analysis, we found that primate-specific endogenous retroviruses (ERVs) are an abundant source of enhancers that mediate transcriptional dysregulation in cancer. In colorectal cancer and other epithelial tumors, AP1 signaling drives aberrant activation of enhancers derived from the primate-specific ERV family LTR10. CRISPR studies revealed that LTR10 elements control colorectal cancer-specific gene expression at multiple loci associated with tumorigenesis. Within the human population, individual LTR10 elements show extensive structural variation due to repeat instability of an internal variable number tandem repeat (VNTR) region that affects AP1 binding. Our findings reveal that ERV-derived enhancers link oncogenic signaling to transcriptional dysregulation and shape the evolution of cancer-specific regulatory networks.
2021-10-31 | GSE186608 | GEO