Progressive heterogeneity of cancer-initiating cells revealed by quantitative clonal analysis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA865696 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20789652_1.fastq.gz | Fastqsanger.gz | |||
| SRR20789652_2.fastq.gz | Fastqsanger.gz | |||
| SRR20789653_1.fastq.gz | Fastqsanger.gz | |||
| SRR20789653_2.fastq.gz | Fastqsanger.gz | |||
| SRR20789654_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Different cellular compartments within a tissue present distinct cancer-initiating capacity. Current approach to dissect cellular heterogeneity in cancer-initiating capacity requires a well-understood tissue lineage hierarchy and highly-specific promoters, which are lacking for most tissues. Here, utilizing a genetic tool called Mosaic Analysis with Double Markers (MADM), we induced scattered GFP-labeled single mutant cells in a broad category of cell types and quantitatively traced their expansion at clonal level, to pinpoint cells susceptible for cancer initiation within under-defined tissues. We dissected the heterogeneous cancer-initiating capacity of fallopian tube Pax8+ cells, which are thought to be the origin for high-grade serous ovarian cancer. We revealed that only a rare primitive subset enriched in the fimbriae can fuel ovarian cancer initiation, and oncogenic mutations exaggerate their intrinsic potential and bias their differentiation for further progression. Collectively, we demonstrated a scheme to dissect cellular heterogeneity in cancer-initiating capacity in tissues lacking established lineage hierarchy.
2022-08-06 | GSE210409 | GEO
Project description:The existence of clonal heterogeneity of mantle cell lymphoma based on genomic aberration evaluated by log2 ratio(clinical samples)
2012-07-30 | E-MTAB-1076 | biostudies-arrayexpress
Project description:Genetic heterogeneity is an important feature of solid tumors, however it is often assumed that most cancer cell lines are genetically homogeneous. A disparity in genetic complexity between cell lines and the disease they model could result in problems such as in vitro preclinical experiments overstating the effectiveness of putative therapeutics. We therefore derived clonal sublines by single cell cloning of in house derived early passage melanoma cell lines (LM-MEL-series), and compared their genomes to each other and the parental cell line using Illumina 610-Quad SNP arrays.
2013-09-08 | E-MTAB-1753 | biostudies-arrayexpress
Project description:Heterogeneity and evolution in acute myeloid leukemia initiating cells
| PRJNA520913 | ENA
Project description:Little is currently known about the heterogeneity of leukemic initiating cells and how they evolve during AML disease progression. AML exhibits extremely few DNA mutations (an average of 13 per patient); therefore, it is likely that RNA based changes also play crucial roles in the development and progression of AML. We have optimized a method to robustly and cost-effectively perform single cell RNA sequencing on AML initiating cells (CD34+CD38-CD45RA+CD90-Lin-7AAD-). We completed a study on serial diagnosis/relapse samples from five AML patients, which revealed strong evidence of the evolution of RNA based changes in AML initiating cells.
2019-05-01 | GSE126068 | GEO
Project description:Human tumours show a high level of clonal heterogeneity that contributes to malignant progression and metastasis, but the processes that influence the timing of metastatic dissemination of subclones are unknown. Here, we have used whole exome sequencing of 98 matched benign, malignant, and metastatic skin tumours from genetically heterogeneous mice to demonstrate that most metastases disseminate synchronously from the primary tumour, but then evolve separately, acquiring an additional set of mutations during growth at distant sites. Shared mutations between primary carcinomas and their matched metastases have the distinct A>T signature of the initiating carcinogen Dimethylbanzanthracene (DMBA), but non-shared mutations are primarily G>T or C>T substitutions, associated with oxidative stress. We found recurrent point mutations in several hundred genes, including several in the Ras (Hras, Kras, and Pik3ca) pathway. We propose that carcinogen-driven mouse tumour models can aid our understanding of the forces that shape clonal and genetic evolution of human cancers.
2015-10-11 | GSE63967 | GEO
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:All cancers emerge following a period of clonal selection and subsequent clonal expansion. Whilst the evolutionary principles imparted by genetic intra-tumour heterogeneity (ITH) are becoming increasingly clear, little is known about the non-genetic mechanisms that contribute to ITH and malignant clonal fitness. Using SPLINTR, a synthetic expressed barcoding strategy, in three clinically relevant mouse models of acute myeloid leukaemia (AML) we find that malignant clonal dominance is a stable and heritable property that is facilitated by the repression of antigen presentation and the increased expression of Slpi, a leukocyte protease inhibitor that has not previously been characterised in AML. Increased transcriptional heterogeneity is a consistent feature enabling clonal fitness in diverse tissue / immune microenvironments and in the context of clonal competition between genetically distinct clones within a uniform microenvironment. Compared to extramedullary sites, leukaemia initiating capacity is most enriched in malignant cells resident within the bone marrow microenvironment and leukaemia stem cells (LSC), like normal haematopoietic stem cells, display heritable clone-intrinsic properties of high, and low clonal output that contribute to the overall tumour mass. Finally, we demonstrate that clonal output does not dictate sensitivity to chemotherapy and both high and low output LSC clones retain marked cellular plasticity enabling them to survive potent therapeutic challenge and persist as minimal residual disease. Together these data provide fundamental insights into the non-genetic transcriptional processes that underpin malignant clonal fitness which may inform future therapeutic strategies.
2021-11-08 | GSE161673 | GEO
Project description:Intratumoral heterogeneity and clonal evolution induced by HPV integration
| PRJNA1006805 | ENA
Project description:All cancers emerge following a period of clonal selection and subsequent clonal expansion. Whilst the evolutionary principles imparted by genetic intra-tumour heterogeneity (ITH) are becoming increasingly clear, little is known about the non-genetic mechanisms that contribute to ITH and malignant clonal fitness. Using SPLINTR, a synthetic expressed barcoding strategy, in three clinically relevant mouse models of acute myeloid leukaemia (AML) we find that malignant clonal dominance is a stable and heritable property that is facilitated by the repression of antigen presentation and the increased expression of Slpi, a leukocyte protease inhibitor that has not previously been characterised in AML. Increased transcriptional heterogeneity is a consistent feature enabling clonal fitness in diverse tissue / immune microenvironments and in the context of clonal competition between genetically distinct clones within a uniform microenvironment. Compared to extramedullary sites, leukaemia initiating capacity is most enriched in malignant cells resident within the bone marrow microenvironment and leukaemia stem cells (LSC), like normal haematopoietic stem cells, display heritable clone-intrinsic properties of high, and low clonal output that contribute to the overall tumour mass. Finally, we demonstrate that clonal output does not dictate sensitivity to chemotherapy and both high and low output LSC clones retain marked cellular plasticity enabling them to survive potent therapeutic challenge and persist as minimal residual disease. Together these data provide fundamental insights into the non-genetic transcriptional processes that underpin malignant clonal fitness which may inform future therapeutic strategies.
2021-11-08 | GSE161672 | GEO