Estimation of rearrangement phylogeny for cancer genomes (original) (raw)

1. Erin D. Pleasance2,
2. Scott Newman3,
3. Fengtang Yang1,
4. Beiyuan Fu1,
5. Serena Nik-Zainal1,
6. David Jones1,
7. King Wai Lau1,
8. Nigel Carter1,
9. Paul A.W. Edwards3,
10. P. Andrew Futreal1,
11. Michael R. Stratton1,4 and
12. Peter J. Campbell1,5
13. 1Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom;
14. 2Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada V5Z 4S6;
15. 3Department of Pathology and Hutchison/MRC Research Centre, University of Cambridge, Cambridge CB2 0XZ, United Kingdom;
16. 4Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom;
17. 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.

• Received November 26, 2010.

• Accepted June 29, 2011.

• Copyright © 2012 by Cold Spring Harbor Laboratory Press

Freely available online through the Genome Research Open Access option.