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 24 for “"Driver mutation"”.
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Quantitative Analyses of Normal and Precancerous Somatic Evolution in Human Tissues
… cell of origin whose lineage accumulates somatic mutations in a step-wise manner over time. The evolutionary process towards cancer development is dynamic and the earliest mutation may arise decades before the onset for some cancers. This calls for a quantitative approach for probing early cancer …
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Inferring context-specific essentiality networks using large-scale CRISPR-KO screens
… genes important in the context of cancer driver mutations and tissue of origin by modelling important properties of CRISPR knockout data. I validated the performance using simulated data and performed various sanity checks, in the absence of a gold standard benchmark. When analysing …
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Somatic evolution in normal human endometrium
… enabled identification and characterisation of driver mutations, provided insights into the tumour burdens and underlying mutational processes, sub-clonal diversification and tumour heterogeneity. However, all cancers arise from cells that were once normal. Over time, they acquired certain …
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Exploring the role of the arginine-methylation writer-reader pair PRMT5/SND1 in JAK2-mutant myeloproliferative neoplasms
… are limited. Discovered in 2005, the JAK2V617F mutation is the most common driver mutation in BCR-ABL negative MPNs, resulting in constitutive activation of the JAK2 protein and the JAK-STAT signaling pathway. A role for the methyltransferase activity of Protein Arginine Methyltransferase 5 …
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Integrated Machine Learning and Bioinformatics Approaches for Prediction of Cancer-Driving Gene Mutations
<p>Cancer arises from the accumulation of somatic mutations and genetic alterations in cell division checkpoints and apoptosis, this often leads to abnormal tumor proliferation. Proper classification of cancer-linked driver mutations will considerably help our understanding of the molecular …
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Regulation of Ciz1 by Cyclin A-Cyclin Dependent Kinase 2 (CDK2) mediated phosphorylation
… have important implications for its role as a driver mutation in cancer biology.
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Inferring Clonal Dynamics in Blood using Single-Cell Measurements
… driven most frequently by the JAK2-V617F mutation, which arises in a single hematopoietic stem cell (HSC) and ultimately dominates the normal process of blood cell production. Although all patients carry the same driver mutation, they still branch into three distinct disease …
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ASCL2 Positive Tumor Cells Modulate the Response of Metastatic Colorectal Cancer to MAPK-Targeting Therapy
… expression increases with therapy independent of driver mutation or treatment regimen. Characterization of ASCL2<sup>+</sup> phenotype revealed a dynamic, proliferative, stem-like cell state with increased tolerance to MAPKi therapy. Additionally, MAPKi therapy resulted in tumor cell induction of …
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Somatic mosaicism in development and paediatric cancer
… trillions of cells in adulthood, these somatic mutations are acquired throughout life either via endogenous errors in DNA replication or environmental DNA damage factors. Most of these somatic mutations land in the vast noncoding intergenic regions of the genome, marking cell lineage but having …
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The evolutionary dynamics of clonal haematopoiesis and its progression to acute myeloid leukaemia
… a consequence of serial acquisition of somatic driver mutations; a process that starts many years, or even decades, before diagnosis. This raises the prospect that early detection of ‘pre-leukaemic’ mutations could be used to identify individuals at high risk of developing AML, in whom early …
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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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The natural history of clonal haematopoiesis
Introduction Human cells acquire somatic mutations throughout life, some of which can drive clonal expansion. Such expansions are frequent in the haematopoietic system of healthy individuals and have been termed clonal haematopoiesis (CH). While CH predisposes to myeloid neoplasia and other …
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Genetic dissection of EGFRvIII brain and spinal mouse gliomas through whole-exome sequencing and in vivo piggyBac mutagenesis forward genetic screening
… is poorly understood. EGFRvIII is a common driver mutation in brain gliomas; it is unclear when this is acquired during glioma evolution and what its cooperative genetic drivers are. Here, we show that EGFRvIII initiates gliomagenesis in vivo; EGFRvIII leads to glioma precursors in the …
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Using Tissue Morphology to Infer Intra-Tumor Variation in Molecular State and Response
… the extent to which intra-tumor variation in key driver genes, BAP1, PBRM1, and SETD2, can be inferred purely from the analysis of histopathology slides. Our work demonstrated for the first time that the morphology-genetics relationship was powerful enough for inference of intra-tumor …
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New molecular and cellular aspects of mutant calreticulin in Myeloproliferative Neoplasms
… role as a calcium (Ca2+) buffering chaperone. Mutations in CALR exon 9 have been identified in essential thrombocythemia and primary myelofibrosis, two myeloproliferative neoplasms (MPNs) characterised by megakaryocyte hyperplasia. Despite the large body of research built around CALR mutations, …
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Detection of the calreticulin type 1 and type 2 mutations in a group of myeloproliferative neoplasm patients using molecular methods
… (PMF) or myelofibrosis (MF). In 2013, somatic mutations at exon 9 of CALR, the gene that encodes for calreticulin, were discovered through whole-exome sequencing and targeted re-sequencing in patients with MPNs. Among these mutations, more than 80% of CALR mutated patients possessed one of only …
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Clonal haematopoiesis of indeterminate potential and the role of inflammation in its association with atherosclerosis
… which haematopoietic stem cells acquire somatic mutations, leading to clonal expansion and aberrant cellular functions. CHIP has been suggested to drive CVD via increased IL-1β from mutant clonal macrophages, but how this can be true for mutations in multiple unrelated genes is unclear. …
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Concomitant Inhibition of Flt3 and Mcl-1 In Flt3 Mutated Acute Myeloid Leukemia
… cells. FLT3 internal tandem duplication (ITD) mutations are common in leukemia and have been observed in up to a third of newly diagnosed AML patients. FLT3-ITD have been implicated as a driver mutation partly responsible for disease progression and associated with increased risk of relapse and …
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Clonal dynamics of haematopoiesis across the human lifespan
… perturbations on haematopoietic stem cell mutation burden and clonal dynamics. To answer the ageing question, I have sequenced 3579 genomes from single-cell-derived colonies of haematopoietic stem cell/multipotent progenitors (HSC/MPPs) from 10 haematologically normal subjects aged 0-81 …
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Does inappropriate DNA replication provide a mechanism for the de novo acquisition of drug resistance?
EGFR is the most common driver mutation in non-small cell lung cancer (NSCLC) and is a common drug target across several cancers. Targeted therapeutics such as those that target EGFR (e.g. Osimertinib) have brought significant patient benefit, however ultimately patients tumours develop resistance …
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