Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 32 for “"clonal evolution"”.
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Modeling Clonal Evolution with Branching Processes
Clonal evolution in tumorigenesis assumes a tumor arises from a single ancestor cell followed by a sequence of mutations that increase fitness in clones. Waves of clonal expansions take place with each new mutation contributing to the selection of the cell. Not all mutations affect a clone's growth …
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Rational drug combinations design against intratumoral heterogeneity and clonal evolution
Cancer is a clonal evolutionary process. This results in complex clonal architecture and intratumoral heterogeneity in each patient. This also presents challenges for effective therapeutic intervention - with constant selective pressure to induce or select pre-existing resistant subclones toward …
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Illuminating Clonal Dynamics: Development and Use of a High-Throughput Cellular Barcoding System to Track Clonal Evolution
It is increasingly recognized that tracking the clonal dynamics of large populations is important in understanding aspects of cancer and stem cell biology. Attempts to track the contributions of individual cells to the clonality of large homogenous populations, however, have been constrained by …
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Multidrug-Resistant Hepatitis B Virus Resulting From Sequential Monotherapy With Lamivudine, Adefovir, and Entecavir: Clonal Evolution During Lamivudine Plus Adefovir Therapy
… remains uncertain. This study investigated the evolution of MDR HBV strains developed from sequential monotherapy with lamivudine (LAM), adefovir (ADV), and entecavir (ETV) during LAM plus ADV salvage therapy. METHODS: Sera were obtained from 6 patients who had developed sequential resistance to …
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Differentially expressed genes in oesophageal cancer
… a multistep process of genomic instability of clonal evolution. Several oncogenes, tumour suppressor genes and transcription factors have been shown to be altered in oesophageal cancer. Their role however, in the development and/or susceptibility to the development of oesophageal cancer is …
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Longitudinal Clonal Lineage Dynamics and Functional Characterization of Pancreatic Cancer Chemo-Resistance and Metastasization
… By dissecting tumors and characterizing clonal lineages, we are better understanding the intricacies of tumor evolution. Tumors are represented by the presence of and dynamic interactions amongst clonal lineages. Each lineage and each cell contributes to tumor dynamics through intrinsic …
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Investigating the properties of cancer stem cells and epithelial to mesenchymal transition in human prostate cancer
… model of cancer progression. Contrary to the clonal evolution model, the cancer stem cell hypothesis postulates that, akin to normal tissues, tumours are hierarchical and only a rare subpopulation of cells, so-called “cancer stem cells” (CSCs), possess the unique biological properties required …
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Investigating Invasion In Ductal Carcinoma In Situ With to pographical Single Cell Genome Sequencing
… in which it is possible to delineate genomic evolution during invasion because of the presence of both in situ and invasive regions within the same sample. While laser capture microdissection studies of DCIS-IDC examined the relationship between the paired in situ (DCIS) and invasive (IDC) …
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Statistical Methods For Resolving Intratumor Heterogeneity With Single-Cell Dna Sequencing
… heterogeneity plays a role in the process of clonal evolution that underlies tumor progression and treatment resistance. Single-cell DNA sequencing is a promising experimental method for studying intratumor heterogeneity, but brings unique statistical challenges in interpreting the resulting …
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Evolution of the genome in myeloproliferative neoplasms and the methylome in blood
… to answer questions pertaining to genomic evolution in myeloproliferative neoplasms (MPNs) and identify changes in the methylome of blood with age and in the context of driver mutations. In the first study, serial sequencing of bulk samples from 30 patients with MPN coupled with clinical …
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Comprehensive Analysis of the Molecular Underpinnings of Pediatric Glioma
… but heterogeneity of many accessory alterations. Clonal evolution modelling uncovered that H3 p.K27M was the most frequent initiating event in DIPG, but universally required an obligate molecular event, most often a TP53 mutation, to promote tumorigenesis. In an effort to understand the molecular …
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Evaluations and Consequences of Tumour Evolution
… capabilities of cancer. By the principles of clonal evolution, cancer development is characterized by the acquisition of advantageous driver mutations followed by expansion of the corresponding subclonal lineage, resulting in varying degrees of intra-tumour heterogeneity. Thus, the cancer …
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Clinical Utility and Impact of Targeted Nucleic Acid Sequencing in Myeloid Malignancies and Precursor Lesions
… several myeloid precursor lesions, such as clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenias of undetermined significance (CCUS), have been linked to the development of myeloid malignancies. We propose that universal implementation of NGS in cases of suspicious or …
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Orthogonal Comparison of Nuclear and Mitochondrial Clonal Architectures in Hematologic Malignancies
… hematopoietic differentiation and promote clonal expansion. Understanding how these mutations arise and evolve is essential for improving diagnosis, prognosis, and treatment stratification. Current methods are limited by either restricted genomic coverage (targeted panels) or low throughput …
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Investigating Metastatic Lineage In Colorectal Cancer By Single Cell Dna Sequencing
… survival rate). Understanding the CRC tumor evolution may provide valuable insights on how to improve treatment in patients with mCRC. However, the genomic basis of metastasis has been difficult to study, in part due to the extensive intratumor heterogeneity at both the primary and metastatic …
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The Role of SOX2 in Colon Cancer Progression
… In effect, high SOX2 expression causes clonal evolution of APC mutant CRC cells from a state of high Wnt dependency to a state of low Wnt dependency in the process making such cells resistant to Wnt inhibitor therapy. Enhanced SOX2 transcriptional activity was associated with increased …
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Array based genetic profiling of chronic lymphocytic leukemia
… included follow-up samples (n=43) to investigate clonal evolution, which showed that patients with unmutated immunoglobulin heavy chain variable (IGHV) genes and treated patients with mutated IGHV genes often gained novel aberrations. In paper III, high-density screening revealed a different …
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EVALUATION OF THE RISK OF SECONDARY LEUKEMIAS IN CANCER SURVIVORS
… Chemotherapy may also play a role in increasing clonal hematopoiesis (CH), a clinical entity associated with a higher risk of developing hematological malignancies. Moreover, the presence of germline mutations in cancer predisposing genes can increase the risk of t-MNs. Our hypothesis is that …
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Sperm sequencing reveals extensive positive selection in the human germline
… variation, making them crucial in the study of evolution and disease. The majority (~80%) of germline mutations in humans are paternal in origin. However, direct observation of mutations in sperm, the gametes of the paternal germline, has been limited by the need for a low error rate sequencing …
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Insights into Neuroblastoma Initiation and Disease Progression Through integrative Genomics and Epigenomics
… Bayesian statistical modeling to understand the clonal evolution that occurs between diagnosis and relapse. Part 1: Neuroblastoma is a pediatric malignancy that typically arises in early childhood, and is derived from the developing sympathetic nervous system. A previous genome-wide association …
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