Abstract

Accurate reconstruction of the evolutionary history of cancer in the patient and quantification of intra-tumour heterogeneity (ITH) are current challenges in cancer genomics. Genomic rearrangements are thereby of particular importance, but notoriously difficult to deal with computationally. The accuracy of tree inference from genomic rearrangements further depends on the quality of the phasing of copy-numbers: the assignment of major and minor copy-numbers to the two physical parental alleles. So far, phasing has been done using evolutionary criteria alone, a heuristic and computationally expensive procedure which impedes probe-level resolution tree reconstruction.

I will give an overview of the challenges and current state of research in reconstructing cancer trees from copy-number data. Results from our clinical studies demonstrate how ITH is associated with chemotherapy resistance in the clinic. I will further illustrate the importance of haplotype- specific copy-number assignment and show how the common genetic background between multiple samples from the same patient can be used to accurately phase copy-number data. This is a crucial step towards probe-level resolution tree inference on genomic rearrangement events in cancer and exact quantification of genetic heterogeneity for routine applications in translational cancer research.