Estimation of rearrangement phylogeny for cancer genomes

Chris D. Greenman; Erin D. Pleasance; Scott Newman; Fengtang Yang; Beiyuan Fu; Serena Nik-Zainal; David Jones; King Wai Lau; Nigel Carter; Paul A.W. Edwards; P. Andrew Futreal; Michael R. Stratton; Peter J. Campbell

doi:10.1101/gr.118414.110

Estimation of rearrangement phylogeny for cancer genomes

¹Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom;
²Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada V5Z 4S6;
³Department of Pathology and Hutchison/MRC Research Centre, University of Cambridge, Cambridge CB2 0XZ, United Kingdom;
⁴Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom;
⁵Department of Haematology, Cambridge University, Cambridge CB2 2XY, United Kingdom

↵6 Present address: Department of Computing, University of East Anglia, Norwich NR4 7TJ, UK; and The Genome Analysis Centre, Norwich Research Park, Norwich NR4 7UH, UK.

Abstract

Cancer genomes are complex, carrying thousands of somatic mutations including base substitutions, insertions and deletions, rearrangements, and copy number changes that have been acquired over decades. Recently, technologies have been introduced that allow generation of high-resolution, comprehensive catalogs of somatic alterations in cancer genomes. However, analyses of these data sets generally do not indicate the order in which mutations have occurred, or the resulting karyotype. Here, we introduce a mathematical framework that begins to address this problem. By using samples with accurate data sets, we can reconstruct relatively complex temporal sequences of rearrangements and provide an assembly of genomic segments into digital karyotypes. For cancer genes mutated in rearranged regions, this information can provide a chronological examination of the selective events that have taken place.

Footnotes

↵7 Corresponding author.

E-mail C.Greenman{at}uea.ac.uk.
[Supplemental material is available for this article.]
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.118414.110.