Ontology highlight
ABSTRACT:
PROVIDER: PRJNA816347 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Clonal diversity contributes to treatment resistance and cancer recurrence. Precise delineation of clonal substructure is essential to understand the resistance mechanism, however, bulk DNA sequencing cannot accurately resolve the complex clonal architectures. Here we report the single-cell DNA sequencing of 123 acute myeloid leukemia (AML) patients and provide cell-level evidence of co-occurrence and mutual exclusivity among driver mutations. Reconstruction of tumor phylogeny uncovers linear and branching clonal evolution patterns, with the latter involving functional convergence. Single-cell DNA sequencing of xenotransplanted samples reveales clonal diversity in leukemia initiating cell populations. Simultaneous single-cell profiling of mutations and cell surface proteins provides cellular genotype-phenotype associations. Analysis of longitudinal samples visualizes the behavior of each individual clone in response to therapy, illustrating the underlying evolutionary process of therapeutic resistance and disease recurrence. Together, these data portray clonal diversity, architecture, and evolution of AML, and highlight their clinical relevance in the era of precision medicine.
2020-09-08 | GSE156934 | GEO
Project description:Genome-wide DNA methylation screening was performed using the Infinium MethylationEPIC BeadChip in 49 fresh-frozen tissue samples and 31 formalin-fixed paraffin-embedded tissue samples obtained from surgically resected materials of patients with endometrioid endometrial cancer.
2022-11-09 | GSE178610 | GEO
Project description:Little is known of the genetic architecture of cancer at the subclonal and single cell level or in the stem-like cells responsible for cancer clone maintenance and propagation. We have examined this issue in ALL in which ETV6-RUNX1 gene fuson is an early or initiating genetic lesion followed by a modest number of driver copy number alterations. By multiplexing FISH probes for these mutations, up to eight genetic abnormalities can be detected in single cells, a genetic signature of sub-clones identified and a composite picture of sub-clonal architecture and putative ancestral trees assembled. Sub-clones in ALL have variegated genetics and complex, non-linear or branching evolutionary histories. CNA are independently and recurrently acquired in sub-clones of individual patients, and in no preferential order. Clonal architecture is dynamic and changes in the lead up to a diagnosis and in relapse. Leukaemic stem cells, assayed by transplantation in NOD/SCID IL2Rgamma deficient mice, are also genetically variegated, mirroring sub-clonal patterns. These findings have significant implications for the cancer stem cell concept, for interpretation of cancer genome data and for therapeutic targetting in cancer.
2010-12-16 | GSE24412 | GEO
Project description:Little is known of the genetic architecture of cancer at the subclonal and single cell level or in the stem-like cells responsible for cancer clone maintenance and propagation. We have examined this issue in ALL in which ETV6-RUNX1 gene fuson is an early or initiating genetic lesion followed by a modest number of driver copy number alterations. By multiplexing FISH probes for these mutations, up to eight genetic abnormalities can be detected in single cells, a genetic signature of sub-clones identified and a composite picture of sub-clonal architecture and putative ancestral trees assembled. Sub-clones in ALL have variegated genetics and complex, non-linear or branching evolutionary histories. CNA are independently and recurrently acquired in sub-clones of individual patients, and in no preferential order. Clonal architecture is dynamic and changes in the lead up to a diagnosis and in relapse. Leukaemic stem cells, assayed by transplantation in NOD/SCID IL2Rgamma deficient mice, are also genetically variegated, mirroring sub-clonal patterns. These findings have significant implications for the cancer stem cell concept, for interpretation of cancer genome data and for therapeutic targetting in cancer. Mononuclear cells were isolated at diagnosis of ALL for patient #3 and #7. Transplantation of 2 000 - 2 000 000 unsorted leukaemia cells was performed by intra-tibial injection into 7 - 14 week old NOD/SCID IL2Rgamma deficient mice. Mice were sacrificed when peripheral blood engraftment was >2%. An equivalent of 2 000 - 200 000 CD45 cells were used for serial transplantation. DNA was extracted from mononuclear cells at initial diagnosis and after second transplantation. Copy number analysis of Affymetrix 500K SNP arrays was performed in CNAG 3.0 for patients #3 and #7 at initial diagnosis and after second transplantation. Reference files were 9 samples from leukemia in remission.
2010-12-16 | E-GEOD-24412 | biostudies-arrayexpress
Project description:We examined ATLL using archived fresh frozen tissue after the biopsy by single-cell RNA sequencing (scRNA-seq) with T-cell receptor (TCR) clonal analysis. Highly clonal tumor cells showed multiple activating pathways, suggesting dynamic evolution of the malignancy. Dissecting diverse cell types comprising the TME led to the identification of a novel subset of cancer-associated fibroblast which showed enriched epidermal growth factor receptor (EGFR)-related transcripts.
2022-03-24 | GSE195674 | GEO
Project description:Fresh frozen Melanoma patient samples were profiled on Affymetrix GeneChip Mapping 100K Set Arrays
2013-10-15 | GSE41592 | GEO
Project description:Patients with treatment-refractory pancreatic cancer often succumb to widespread systemic metastases; however, the transcriptomic heterogeneity that underlies recalcitrance to therapy remains understudied, particularly in the spatial context. We constructed high-resolution spatial maps of transcriptional heterogeneity, clonal architecture and lineage plasticity using spatially resolved transcriptomics (SRT) from 13 primary cancers and 36 corresponding liver, lung, and peritoneal metastases, collected via a rapid (“warm”) autopsy program. To validate findings from our SRT dataset at single-cell resolution, we performed CosMX SMI profiling (Nanostring) on 7 samples from 3 patients, including primary and/or liver metastasis.
2025-02-21 | GSE277782 | GEO
Project description:Every year more than 42,000 women die of endometrial cancer, mainly due to recurrent or metastatic disease. The presence of tumor infiltrating lymphocytes (TILs) as well as progesterone receptor (PR) positivity has been correlated with improved prognosis. This study describes two mechanisms by which progesterone inhibits metastatic spread of endometrial cancer: by stimulating T-cell infiltration and by inhibiting epithelial-to-mesenchymal cell transition (EMT). Paraffin sections from patients with (n=9) or without (n=10) progressive endometrial cancer (recurrent or metastatic disease) were assessed for the presence of CD4+ (helper), CD8+ (cytotoxic) and Foxp3+ (regulatory) T-lymphocytes and PR expression. Progressive disease was observed to be associated with significant loss of TILs and loss of PR expression. Frozen tumor samples, used for genome-wide expression analysis, showed significant regulation of pathways involved in immunosurveillance, EMT and metastasis. For a number of genes, such as CXCL14, DKK1, DKK4 and WIF1, quantitive RT-PCR was performed to verify down regulation in progressive disease. To corroborate the role of progesterone in regulating invasion, Ishikawa (IK) endometrial cancer cell lines stably transfected with PRA (IKPRA), PRB (IKPRB) and PRA+PRB (IKPRAB) were cultured in the presence/absence of progesterone (MPA) and used for genome-wide expression analysis, Boyden- and wound healing migration assays, and IHC for known EMT makers. IKPRB and IKPRAB cell lines showed MPA induced inhibition of migration and loss of the mesenchymal marker vimentin at the invasive front of the wound healing assay. Furthermore, pathway analysis of significantly MPA-regulated genes showed significant down regulation of important pathways involved in EMT, immunesuppression and metastasis: such as IL6-, TGF-β and Wnt/β-catenin signalling. Intact progesterone signaling in non-progressive endometrial cancer seems to be an important factor stimulating immunosurveillance and inhibiting transition from an epithelial to a more mesenchymal, more invasive phenotype. From 4 non-progressive and 4 progressive patients, snap-frozen endometrial cancer tumor specimens were used for microarray analysis. Gene expression data of progressive disease was compared with non-progressive disease.
2012-01-26 | E-GEOD-29436 | biostudies-arrayexpress
Project description:Available genetically-defined cancer models are limited in genotypic and phenotypic complexity and underrepresent the heterogeneity of human cancer. Herein, we describe a combinatorial genetic strategy applied to an organoid transformation assay to rapidly generate diverse, clinically relevant models of bladder and prostate cancer. Importantly, the clonal architecture of the resultant tumors can be resolved using single-cell or spatially resolved next-generation sequencing to uncover polygenic drivers of cancer phenotypes.
2023-12-01 | GSE231543 | GEO