Timing of chromosomal alterations during tumour development

Abstract

During cancer development, tumour cells will accumulate a lot of both somatic point mutations and copy number alterations. It is not unusual that affected genes have a copy number that differs from the usual two. Due to the loss of DNA repair mechanisms the cells can mutate independent from each other which gives rise to different subclones within the tumour. A tumour cell and its future daughter cells that gets an advantage in cell division speed compared to its competing neighbours, will eventually make up a large portion of the tumour. All the mutations that the subclone’s most recent common ancestor acquired until the expansion will be shared across the subclone. In this project, we have developed a method using the mutation frequencies from publicly available whole genome sequencing data, to quantify the amount of competing subclones in a sample and determining the time to its copy number duplications. This method could be further developed to be an extension to regular copy number analysis. A heterogeneous tumour can grow faster and be more resistant to treatment. Therefore, it is important to learn more about cancer development and get a greater understanding of the order in which copy number alterations occur

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