Rearrangements and Duplications in Tumor Genomes

Ben Raphael

Genome rearrangements (e.g. chromosome inversions and translocations) and duplications are commonly observed in tumor cells, and are directly implicated in the progression of some types of cancer. While many individual rearrangements and duplications in tumors have been cataloged, little is known about the detailed architecture of tumor genomes. Recently, an experimental technique called End Sequence Profiling (ESP) has produced high-resolution data about tumor genome structure. We describe computational methods for analyzing ESP data. We formulate the ESP Genome Reconstruction and Amplisome Reconstruction Problems, whose solutions give parsimonious descriptions of rearrangements and duplications in tumor genomes. We describe methods for solving these problems, and illustrate our methods on ESP data from the MCF-7 breast tumor cell line. We derive both a putative architecture of the MCF-7 genome and a putative architecture of a tumor amplisome that is the source for duplicated material in MCF-7.