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 34 for “"Mutational Signatures"”.
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Exploring mutational signatures in human cancers using human cell line models
… of cancer research for a long time, passenger mutational signatures – the imprints of DNA damage and DNA repair processes that have been operative during tumourigenesis – are also biologically informative. Since the inception of the field, many mutational signatures have been uncovered from the …
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An Investigation of Mutational Signatures in the Evolution of Oesophageal adenocarcinoma
An Investigation of Mutational Signatures in the Evolution of Oesophageal adenocarcinoma Sujath Abbas Oesophageal adenocarcinoma (OAC) remains a public health challenge with dismal survival rates and increasing incidence. This PhD study aimed to investigate how mutational processes act across …
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Driver genes, mutational signatures and the timing of mutations in oesophageal adenocarcinoma
… of information regarding the mutations and mutational processes that drive OAC is likely contributing to this. However to understand the development of a cancer it is not enough to simply identify commonly mutated genes, rather it is also crucial to identify the timings at which these …
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Identifying and characterizing hereditary polyposis and colorectal cancer: Mutational signatures of defective base excision repair
Contains fulltext : 239215.pdf (Publisher’s version ) (Open Access)
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Quantifying the pro- and antimutagenic roles of DNA damage and repair
… a range of diseases including cancer. Different mutational processes often leave behind characteristic patterns of mutations, so-called mutational signatures. Mutational signature analysis of tumours has gained a lot of attention recently, because it may reveal carcinogenic exposures and also …
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A comprehensive survey of somatic mutation landscapes in normal human cells
… mutations over a lifetime involves multiple mutational processes, each with distinct mutation patterns, known as mutational signatures. Recent studies have shown that the somatic mutation burden varies between cell types, tissues, organs and individuals. However, due to technical limitations, …
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Mutational processes in normal human tissues
… of somatic mutations is shaped by numerous mutational processes, each generating a distinctive profile of mutations, called a ‘mutational signature’. From mutational signatures, one can infer a history of operating mutational processes that have acted on the genome. Therefore, they can be a …
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Compositional models for mutational signature analysis
… life, or even throughout tumour development. Mutational signatures were introduced as a proxy to quantify the number of mutations created by each mutational process. This thesis focuses on statistical methods for the analysis of such mutational signatures. Crucially, mutational signatures, in …
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Analysis of driver gene mutations in oesophageal squamous cell carcinoma
… By quantifying the contribution of the mutational signatures to the mutation spectrum, we found a relatively high contribution of mutation signature SBS1, SBS2, and SBS13, implicating aging and AID/APOBEC (activation induced cytidine deaminase/apolipoprotein B mRNA editing enzyme …
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Mapping the Genomic Context of Mutagenesis
… 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 mutation patterns by applying non-negative matrix factorisation to catalogues of …
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Germline and somatic mutational processes across the Tree of Life
… control samples with characterised somatic mutational processes, along with a negative control sample to establish the limit of detection. The mutational spectra derived from the detected somatic mutations closely matched the expected profiles of the positive controls, supporting the …
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Elucidating the Multi-omics of Early-Onset Colorectal Cancer
… we investigated the multi-omics of the EOCRC. Mutational signatures are the footprints of endogenous or exogenous exposomal exposures.</p> <p>In the first study, we focused on early-onset rectal cancer (EORC) where the epidemiologic changes are the most concerning. Using whole-genome and RNA …
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The impact of cytotoxic chemotherapy on somatic mutation in normal human cells
… mutagenesis. Patterns of mutations or ‘mutational signatures’ associated with chemotherapy have been seen in patient tumours, in cells exposed to drugs *in vitro*, and in some normal tissue samples from cancer patients. However, a comprehensive study of the impact of chemotherapy on the …
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The mutational landscape of normal urothelium
… clones. Additionally, we identify three novel mutational signatures, one of which is associated with smoking, a major risk factor for bladder cancer the molecular basis for which was previously unknown. Overall, this dissertation provides a tantalising glimpse into the rich and diverse …
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Evolution of the genome in myeloproliferative neoplasms and the methylome in blood
… mutation acquisition. In addition, analysis of mutational signatures highlights mutagenic signals associated with therapy. In the second and more substantial body of work, a novel method to interrogate genome- wide methylation is developed and optimised and I show the steps taken to achieve …
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The Intra-Tumour Heterogeneity Landscape of Human Cancers
… that activity of smoking and UV-light associated mutational signatures goes down as the tumour evolves, while activity of the APOBEC associated signatures goes up.
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Elucidation of the pathways underlying the spectrum of cancers affecting different tissues in lynch syndrome
… expression, pathway enrichment, kinase activity, mutational signatures, and drug sensitivity assessments to characterise cancer subtypes. The study identified PI3-Akt and Wnt signalling as dysregulated in LLS-CRC and LSp-CRC, respectively. Similar analyses in EC and BC revealed that the TGF-beta …
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Multi-omic characterisation of Barrett’s oesophagus reveals a molecular continuum in the progression to oesophageal adenocarcinoma
… BE is highly heterogeneous with regards to mutational load, copy-number aberrations (CNAs) and structural variants (SVs). Mutational signatures are laid down early and persist regardless of progression status. Hence, Cosmic signature 17 (T:A>G:C in a CTT context), the hallmark of OAC, is …
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