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, Rick Tourdot
HMS, Dana Farber
In search of lost time: reconstructing the evolutionary history of cancer genomes

Abstract:  Chromosomal abnormalities are a hallmark feature of cancer genomes. In contrast to point mutations that mostly accumulate gradually during tumor development, chromosomal rearrangements are often generated episodically and manifest as clusters (or complex rearrangements). Such complexity makes it extremely difficult to identify patterns of chromosomal rearrangements or infer the history of rearrangement accumulation. In this talk, I will discuss our recent progress towards solving this problem based on three ideas. The first is to combine haplotype phasing and allelic copy-number analysis to determine the DNA copy number of each parental homolog. The second is to combine haplotype copy number and discordant read pairs to construct the sequence of rearranged chromosomes. Finally, we use knowledge from in vitro cell biology experiments to recognize unique rearrangement patterns. I will also discuss strategies to infer the timing of mutational events.