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 27 for “"cancer genomes"”.
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Structural determinants of mutability across cancer genomes
Cancer is a group of diseases which are characterised and actuated by somatic mutations. In cancer the distribution of mutations across the genome is inhomogeneous, with genomic and epigenomic features influencing mutational patterns. Previous studies have indicated that chromatin organization and …
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The structure and evolution of breast cancer genomes
… recurrent fusion genes in prostate and lung cancer proved to be iconic examples as they indicated that important gene fusions are found in the common epithelial cancers also. Breast cancers often display extensive structural and numerical chromosome aberration and have among the most complex …
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Algorithms for analyzing complex structural variations in cancer genomes
Analysis of somatic alterations in cancer genomes has been accelerated through the rapid growth of the quantity, quality and depth of data generated by next-generation sequencing (NGS). Previously most of cancer genome studies were focusing on single nucleotide variations (SNVs), small insertions …
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Computational methods for the detection of somatic structural variants in cancer genomes using long-read sequencing
… informing the diagnosis and treatment of human cancers. In this thesis, I present SAVANA, a computational method for the analysis of somatic SVs using long-read whole genome sequencing data from tumours and matched normal samples. SAVANA employs machine learning to distinguish true somatic SVs …
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Tumor-penetrating delivery of small interfering RNA therapeutics
Efforts to sequence cancer genomes have begun to uncover comprehensive lists of genes altered in cancer. Unfortunately, the number and complexity of identified alterations has made dissecting the underlying biology of cancer difficult, as many genes are not amenable to manipulation by small …
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TOWARDS AN UNDERSTANDING OF GENETIC SELECTION IN BREAST CANCER
Cancer genomes accumulate chromosomal abnormalities and gene mutations but must maintain the ability to survive in vitro. We sought evidence in breast cancer that genetic selection acts to maintain tumour survival. Analysis of genomes from 243 breast tumours revealed 766 unstable and 812 stable …
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INSIGHTS INTO THE SELECTION AND FUNCTION OF COPY-NUMBER ALTERATIONS DURING CANCER EVOLUTION
Cancer evolution is a complex process mostly driven by genomic instability, including large- and small-scale alterations, such as copy-number alterations (CNAs) or single-nucleotide mutations, respectively. Those alterations play a critical role in tumor development, genetic diversity, and …
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Genome reconstruction and combinatoric analyses of rearrangement evolution
Cancer is often associated with a high number of large-scale, structural rearrangements. In a highly selective environment, some `driver' mutations conferring clonal growth advantage will be positively selected, accounting for further cancer development. Clarifying their nature, as well as their …
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Accurate Identification of Significant Aberrations in Cancer Genome: Implementation and Applications
… Alterations (CNAs) are common events in human cancers. Identifying CNAs and Significant Copy number Aberrations (SCAs) in cancer genomes is a critical task in searching for cancer-associated genes. Advanced genome profiling technologies, such as SNP array technology, facilitate copy number …
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Automatic Tumour Typing based on Patterns of Somatic Passenger Mutations
In cancer, a tumour’s cell of origin is the strongest determinant of its clinical behaviour. While cell of origin is typically clear at the time of diagnosis, 3-5% of cancer patients present with a metastatic tumour and no obvious corresponding primary tumour. Despite advances in molecular testing, …
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Pan-Cancer Analysis of Non-Coding Driver Mutations
Cancers are caused by genomic alterations known as drivers. As drivers have broad applications in precision oncology, their discovery has become one of the central motivations for cancer genomics. At present, the majority of drivers have been found in the ~2% protein-coding regions. Despite an …
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Evaluations and Consequences of Tumour Evolution
Somatic mutations detected in cancer genomes are the result of mutation accumulation since the fertilized egg. Select mutations, as the result of mutagenic processes or defects in DNA damage repair, confer growth advantages by enabling hallmark capabilities of cancer. By the principles of clonal …
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Novel methods in transcriptome analysis using RNA-seq
… created as a result of genome rearrangement in cancer. Some of them play important roles in carcinogenesis, and can serve as diagnostic and therapeutic targets. With more and more cancer genomes being sequenced by next-generation sequencing technologies, we believe an efficient tool for reliably …
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Determining therapeutically actionable genetic interactions in human cancer at scale using multiplexed CRISPR screening
… enabling the selective targeting of gene loss in cancer. This study employed a high-throughput multiplexed combinatorial CRISPR/Cas9 pooled screening approach to systematically identify SL interactions. A novel tRNA-based dual guide expression system was used to construct the Synergy library, …
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Phylogenetic studies into the development of foetal tissues and their neoplastic derivatives
… a century, data have indicated that childhood cancer is rather different, most likely emerging as an aberration of foetal development. This thesis explores how foetal tissues and their neoplastic progeny propagate, focusing specifically on the placenta, germ cell tumours and high-grade midline …
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Mapping the Genomic Context of Mutagenesis
… of genomic mutations leads to the formation of cancer. For this reason, many efforts have been undertaken to characterise mutational processes in terms of their genomic imprints. A particularly successful approach is matrix-based mutational signature analysis, which identifies prototypical …
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Variation-aware algorithms for cancer genome analysis
… explore variation-aware algorithms for analyzing cancer genomes. The scientific community has extensively catalogued millions of mutations present in cancer cells. This information is rarely used during read alignment and variant calling because of a lack of algorithms for doing so. Rediscovering …
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blmp-1 is a Ras-cooperating Tumor Suppressor Gene in Caenorhabditis elegans
… of colorectal, 45% of lung and 90% of pancreatic cancers, activated Ras alone is not sufficient to transform normal cells into cancerous tumors. Additional driver mutations or epigenetic alterations are required to cooperate with the activating Ras mutations in tumorigenesis. In C. elegans, worms …
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Investigating the regulation of APOBEC mutagenesis in cancer
The sequencing of cancer genomes has revealed that cancers harbour recurrent patterns of mutation, known as mutational signatures. One common mutational signature, known as the APOBEC signature, is found in over 70% of cancer types. The APOBEC signature is thought to be mediated by the activity of …
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Functional Analysis of the F-box protein Fbxl17
… have allowed detailed characterisation of cancer genomes and has highlighted the contribution of somatic structural variations to the mutational landscape of epithelial tumours. However, our understanding of the functional consequences of such genome rearrangements remains rudimentary. By …
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