Ontology highlight
ABSTRACT:
PROVIDER: PRJNA631756 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11785240_1.fastq.gz | Fastqsanger.gz | |||
| SRR11785240_2.fastq.gz | Fastqsanger.gz | |||
| SRR11785241_1.fastq.gz | Fastqsanger.gz | |||
| SRR11785241_2.fastq.gz | Fastqsanger.gz | |||
| SRR11785242_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 70 |
Similar Datasets
Project description:Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Understanding of the intratumoral heterogeneity of HCC is instructive for developing personalized therapy and molecular biomarkers. We applied whole exome sequencing to a total of 63 samples from 11 patients to resolve the genetic architecture and subclonal diversification. Notably, spatial genomic diversity was found in all 11 HCC cases, with 33% of the driver mutations being heterogeneous. Temporal dissection of mutational signatures suggested that exogenous and endogenous factors have different contributions in shaping the mutational spectrum during the development of HCC. Moreover, we observed extensive intratumoral epigenetic heterogeneity in HCC, and showed that integrative analysis of both genetic and epigenetic phylogenies could generate more robust resolution of clonal architecture than single profiling approach. Our results also demonstrated prominent epigenetic subclonal diversification even in a stable HCC genome. Together, these findings highlight the widespread intratumoral heterogeneity at both genomic and epigenomic levels in HCC, and provide important molecular foundation for better understanding of the biology and pathogenesis of this malignancy.
2017-03-03 | GSE83691 | GEO
Project description:Activating signaling mutations are common in acute leukemia with KMT2A (previously MLL) rearrangements (KMT2A-R). These mutations are often subclonal and their biological impact remains unclear. Using a retroviral acute myeloid mouse leukemia model, we demonstrate that FLT3ITD, FLT3N676K, and NRAS G12D accelerate KMT2A-MLLT3 leukemia onset. Subclonal FLT3N676K mutations also accelerate disease, possibly by providing stimulatory factors such as Mif. Acquired de novo mutations in Braf, Cbl, Kras, and Ptpn11 were identified in KMT2A-MLLT3 leukemia cells and favored clonal expansion. During clonal evolution, serial genetic changes at the KrasG12D locus was observed, consistent with a strong selective advantage of additional KrasG12D. KMT2A-MLLT3 leukemias with signaling mutations enforced Myc- and Myb transcriptional modules. Our results provide new insight into the biology of KMT2A-R leukemia with subclonal signaling mutations and highlights the importance of activated signaling as a contributing driver in this disease.
2018-05-02 | GSE106714 | GEO
Project description:Cancer evolves dynamically, as clonal expansions supersede or overlap one another, driven by shifting selective pressures, mutational processes and disrupted cancer genes. These processes mark the genome, such that a cancerÕs life history is encrypted in the timing, ploidy, clonality and patterns of somatic mutation. We developed bioinformatic algorithms to decipher this narrative, and applied them to 21 breast cancer genomes. We find that mutational processes evolve across the lifespan of a breast tumor, with cancer-specific signatures of point mutations and chromosomal instability often emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, providing insight into the dynamics of clonal expansion in breast cancer. Most point mutations are found in just a fraction of tumor cells, together with frequent variegation in chromosomal copy number. Every tumor studied here has a dominant subclonal lineage, representing more than 50% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent lineages of cells that are capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis.
2012-06-16 | E-MTAB-1087 | biostudies-arrayexpress
Project description:Cancer evolves dynamically, as clonal expansions supersede or overlap one another, driven by shifting selective pressures, mutational processes and disrupted cancer genes. These processes mark the genome, such that a cancerÕs life history is encrypted in the timing, ploidy, clonality and patterns of somatic mutation. We developed bioinformatic algorithms to decipher this narrative, and applied them to 21 breast cancer genomes. We find that mutational processes evolve across the lifespan of a breast tumor, with cancer-specific signatures of point mutations and chromosomal instability often emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, providing insight into the dynamics of clonal expansion in breast cancer. Most point mutations are found in just a fraction of tumor cells, together with frequent variegation in chromosomal copy number. Every tumor studied here has a dominant subclonal lineage, representing more than 50% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent lineages of cells that are capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis.
2012-06-29 | E-MTAB-1088 | biostudies-arrayexpress
Project description:Functional defects resulting from deleterious mutations can often be restored during evolution by compensatory mutations elsewhere in the genome. Importantly, this process can generate the genetic diversity seen in networks regulating the same biological function in different species. How the options for compensatory evolution depend on the molecular interactions underlying these functions is currently unclear. This dataset, comprising multiple SATAY transposon mutagenesis libraries, was used to examine how gene deletions that compensate for defects in the polarity pathway of Saccharomyces cerevisiae impact the fitness landscape on a genome-wide scale. In total, 12 SATAY libraries were created, consisting of 6 biological replicate experiments of a wild-type strain (yEK19) and 6 biological replicates of a bem1Δbem3Δnrp1Δ mutant (yEK23). For each strain, the letter following the strain name (for example, yEK19a and yEK23a) represents different colonies taken from the same transformation plate during strain construction. Following strain construction, the different replicates of yEK19 and yEK23 were transformed with plasmid pBK549 and multiple colonies were selected from the transformation plate to generate the SATAY libraries. The numbers at the end of each strain name (for example, yEK19a_6 and yEK23a_23) indicate different colonies that were picked from the transformation after the transformation with plasmid pBK549.
2025-10-19 | E-MTAB-15098 | biostudies-arrayexpress
Project description:Activating mutations in kinase/PI3K/RAS signaling pathways are common in acute leukemia with KMT2A rearrangements (KMT2A-R). These mutations are often subclonal and their biological impact remain unclear. Using a retroviral acute myeloid leukemia model, we demonstrate that NRASG12D, FLT3ITD, and FLT3N676K accelerates KMT2A-MLLT3 leukemia onset. Importantly, also the presence of subclonal FLT3N676K in KMT2A-R leukemic cells shorten disease latency, possibly by providing stimulatory factors such as Mif. Acquired de novo mutations in Braf, Cbl, Kras, and Ptpn11 were identified in KMT2A-MLLT3 driven leukemia and favored clonal expansion. KMT2A-MLLT3 leukemia with an activating mutation enforce Myc- and Myb transcriptional modules, whereas KMT2A-MLLT3 leukemias lacking activating mutations displayed upregulation of signal transduction pathways. Our results provide new insight into the biology of KMT2A-R leukemia and highlights the importance of activated signaling as a contributing driver in this disease.
2018-05-02 | PXD008213 | Pride
Project description:During pancreatic cancer progression, heterogeneous subclonal populations evolve in the primary tumor that possess differing capacities to metastasize and cause patient death. However, the genetics of metastasis reflects that of the primary tumor, and PDAC driver mutations arise early. This raises the possibility than an epigenetic process could be operative late. Using an exceptional resource of paired patient samples, we found that different metastatic subclones from the same patient possessed remarkably divergent malignant properties and global epigenetic programs. Global reprogramming was targeted to thousands of large chromatin domains across the genome that collectively specified malignant divergence. This was maintained by a metabolic shift within the pentose phosphate pathway, independent of KRAS driver mutations. Analysis of paired primary and metastatic tumors from multiple patients uncovered substantial epigenetic heterogeneity in primary tumors, which resolved into a terminally reprogrammed state in metastatic lesions. This supports a model whereby driver mutations accumulate early to initiate pancreatic tumorigenesis, followed by a period of subclonal evolution that generates sufficient intra-tumor heterogeneity for selection of epigenetic programs that may increase fitness during malignant progression and metastatic spread. To map the epigenomic landscape of pancreatic cancer progression as it evolves within patients. BS-Seq of 4 patients (A13, A38, A124 and A125). Patient A38 included local peritoneal metastasis and 2 distant metastsis (liver and lung mets). Patient A13 included 2 primary tumors and 1 distant lung metastasis. Each sample has been done with replicates. Patient A124 included 2 primary tumors and 1 normal pancreas.
2016-10-24 | E-GEOD-63123 | biostudies-arrayexpress
Project description:During pancreatic cancer progression, heterogeneous subclonal populations evolve in the primary tumor that possess differing capacities to metastasize and cause patient death. However, the genetics of metastasis reflects that of the primary tumor, and PDAC driver mutations arise early. This raises the possibility than an epigenetic process could be operative late. Using an exceptional resource of paired patient samples, we found that different metastatic subclones from the same patient possessed remarkably divergent malignant properties and global epigenetic programs. Global reprogramming was targeted to thousands of large chromatin domains across the genome that collectively specified malignant divergence. This was maintained by a metabolic shift within the pentose phosphate pathway, independent of KRAS driver mutations. Analysis of paired primary and metastatic tumors from multiple patients uncovered substantial epigenetic heterogeneity in primary tumors, which resolved into a terminally reprogrammed state in metastatic lesions. This supports a model whereby driver mutations accumulate early to initiate pancreatic tumorigenesis, followed by a period of subclonal evolution that generates sufficient intra-tumor heterogeneity for selection of epigenetic programs that may increase fitness during malignant progression and metastatic spread. To map the epigenomic landscape of pancreatic cancer progression as it evolves within patients. Chip-Seq (K27Me3, K36Me3, K9Me2/3, K4Me3 and K27Ac) of 2 patients (A13 and A38) and HPDE cell line. Patient A38 included local peritoneal metastasis and 2 distant metastsis (liver and lung mets), and 6AN treated and DMSO samples for lung matastasis. Patient A13 included 2 primary tumors and 1 distant lung metastasis. Each sample has been done with replicates.
2016-10-24 | E-GEOD-63125 | biostudies-arrayexpress
Project description:To investigate immunoediting at the primary tumour, we used DNA barcoding combined with NGS. By stably integrating EMT6 murine cancer cell line with 5000 unique DNA barcodes (1 barcode per cell), we can trace how barcode (and therefore subclonal) diversity changes over time and after treatment with immunotherapy.
2022-08-02 | GSE210047 | GEO