Application of Phylogenetic Analysis in Cancer Evolution

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2018

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Abstract

Cancer is a major threat to human health and results in 1 in 6 deaths globally. Despite an extraordinary amount of effort and money spent, eradication or control of advanced disease has not yet been achieved. Understanding cancer from an evolutionary point of view may provide new insight to more effective control and treatment of the disease. Cancer as a disease of dynamic, stochastic somatic genomic evolution was first described by Nowell in 1976, and since then researchers have identified clonal expansions and genetic heterogeneity within many different types of neoplasms. The advancement in sequencing technology, especially single-cell sequencing, has open up new frontier by bringing the study of genomes to the cellular level. Phylogenetic analysis, which is a powerful tool inferring evolutionary relationships among various biological species or other entities based upon similarities and differences in their physical or genetic characteristics, has recently been applied to cancer studies and start to show promises in deciphering cancer evolution. However, new challenges have also arisen in experimental design, methodology and interpretation regarding to phylogeny of cancer cells. The overarching theme of this dissertation is to bring phylogenetic analysis to the context of cancer evolution. By using in silico simulations, I show the advantages and disadvantages of different sampling designs for phylogenetic analysis. Although bulk sequencing can hardly recover the topology of phylogenetic trees, I then developed a new method to infer sub-clone spatial distribution utilizing phased haplotypes from bulk sequencing. And lastly, I demonstrate the usage of phylogenetic analysis in breast cancer with multi-regional bulk sequencing and lung cancer with single cell sequencing.

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Ding, Yuantong (2018). Application of Phylogenetic Analysis in Cancer Evolution. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/16897.

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