Evolution of bladder cancer investigated using exome sequencing

Download
index.pdf
2015
Özkurt, Ezgi
Show full item record
170
views
59
downloads
New genome sequencing technologies today allow the study of cancer evolution within individual tissues. In bladder cancer, it is commonly observed that multiple tumours co-occur in a tissue. However, whether these tumours are related (clonal hypothesis) or develop independently but synchronously (field effect hypothesis), was yet unknown. In this study, exome sequencing data was utilized to reveal the origin of multifocal tumours. The data was generated in an experiment where samples from bladder tumour (3 tumour samples per patient) and neighbouring normal mucosa (1 normal sample per patient) from 3 patients were collected and sequenced. The tumour samples were composed of apex and base sections of the tumours. Thousands of single nucleotide variants (SNV) were called in each patient. The phylogenetic trees constructed by SNV datasets of the 2 patients showed a topology consistent with clonal origin hypothesis, with a long shared tumour branch, indicating that the tumours derive from the same origin. The third patient's samples were suspected to be contaminated with neoplastic material, and thus not included in the rest of the analysis. An analysis of SNV types with respect to sequence context revealed that TpC* mutations were particularly enriched on the shared tumour branch, indicative of activity of APOBEC enzymes (single stranded DNA/RNA editing proteins) causing accumulation of TpC* mutations. Thus, it is hypothesized that a period of APOBEC activity led to accumulation of TpC* mutations, some of which included driver mutations that led to tumour formation, and subsequent separation of the tumours in 2 patients.
Cancer., Phylogeny., Bladder, Population genetics.
http://etd.lib.metu.edu.tr/upload/12618849/index.pdf
https://hdl.handle.net/11511/24738
Graduate School of Natural and Applied Sciences, Thesis

Suggestions

Comparative study on antibody immobilization strategies for efficient circulating tumor cell capture
ATES, Hatice Ceren; OZGUR, Ebru; Külah, Haluk (2018-03-01)
Methods for isolation and quantification of circulating tumor cells (CTCs) are attracting more attention every day, as the data for their unprecedented clinical utility continue to grow. However, the challenge is that CTCs are extremely rare (as low as 1 in a billion of blood cells) and a highly sensitive and specific technology is required to isolate CTCs from blood cells. Methods utilizing microfluidic systems for immunoaffinity-based CTC capture are preferred, especially when purity is the prime requirem...
Targeted delivery of CPG-oligodeoxynucleotide to breast cancer cells by poly-amidoamine dendrimer-modified magnetic nanoparticles
Taghavi Pourianazar, Negar; Gündüz, Ufuk; Gündüz, Güngör; Department of Biotechnology (2016)
One major application of nanotechnology in cancer treatment involves designing nanoparticles to deliver drugs, oligonucleotides, and genes to cancer cells. Nanoparticles should be engineered so that they could target and destroy tumor cells with minimal damage to healthy tissues. This research aims to develop an appropriate and efficient nanocarrier, having the ability of interacting with and delivering CpG-oligodeoxynucleotides (CpG-ODNs) to tumor cells. CpG-ODNs activate Toll-like receptor 9 (TLR9), which...
A Framework for gene co-expression network analysis of lung cancer
Akdemir, Erhan; Can, Tolga; Aydın Son, Yeşim; Department of Bioinformatics (2013)
Construction method of a gene co-expression network (GCN) is crucial in medical research aiming to reveal disease related genes. Applied similarity measure and selection of edges that represent significantly co-expressed gene pairs in the network affect directly the elements of a network and so the list of prioritized genes. Pearson correlation coefficient is a commonly used similarity measure to quantify co-expressions of genes due to its simplicity and performance compared to many complex methods. However...
CpG oligodeoxynucleotide- loaded PAMAM dendrimer-coated magnetic nanoparticles promote apoptosis in breast cancer cells
Pourianazar, Negar Taghavi; Gündüz, Ufuk (2016-03-01)
One major application of nanotechnology in cancer treatment involves designing nanoparticles to deliver drugs, oligonucleotides, and genes to cancer cells. Nanoparticles should be engineered so that they could target and destroy tumor cells with minimal damage to healthy tissues. This research aims to develop an appropriate and efficient nanocarrier, having the ability of interacting with and delivering CpG-oligodeoxynucleotides (CpG-ODNs) to tumor cells. CpG-ODNs activate Toll-like receptor 9 (TLR9), which...
Pan-cancer clinical impact of latent drivers from double mutations
Yavuz, Bengi Ruken; Tsai, Chung-Jung; Nussinov, Ruth; Tuncbag, Nurcan (2023-12-01)
Here, we discover potential ‘latent driver’ mutations in cancer genomes. Latent drivers have low frequencies and minor observable translational potential. As such, to date they have escaped identification. Their discovery is important, since when paired in cis, latent driver mutations can drive cancer. Our comprehensive statistical analysis of the pan-cancer mutation profiles of ~60,000 tumor sequences from the TCGA and AACR-GENIE cohorts identifies significantly co-occurring potential latent drivers. We ob...
Citation Formats
E. Özkurt, “Evolution of bladder cancer investigated using exome sequencing,” M.S. - Master of Science, Middle East Technical University, 2015.
METU IIS - Integrated Information Service open@metu.edu.tr