Computational Methods for Analysis of Tumor Clonality and Evolutionary History

  • Gerald GohEmail author
  • Nicholas McGranahan
  • Gareth A. Wilson
Part of the Methods in Molecular Biology book series (MIMB, volume 1878)


Cancer is an evolutionary process. Recent advances in sequencing technologies have allowed us to investigate intratumor heterogeneity at the single nucleotide level. Here, we describe computational methods that use sequencing data to identify genetically distinct tumor subclones and reconstruct tumor evolutionary histories.

Key words

Cancer Next-generation sequencing Heterogeneity Clonal Evolution Phylogeny 


  1. 1.
    Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194(4260):23–28CrossRefGoogle Scholar
  2. 2.
    Burrell RA, Swanton C (2014) The evolution of the unstable cancer genome. Curr Opin Genet Dev 24:61–67. Scholar
  3. 3.
    Lee AJ, Swanton C (2012) Tumour heterogeneity and drug resistance: personalising cancer medicine through functional genomics. Biochem Pharmacol 83(8):1013–1020. Scholar
  4. 4.
    Swanton C (2012) Intratumor heterogeneity: evolution through space and time. Cancer Res 72(19):4875–4882. Scholar
  5. 5.
    Murugaesu N, Wilson GA, Birkbak NJ, Watkins TB, McGranahan N, Kumar S et al (2015) Tracking the genomic evolution of esophageal adenocarcinoma through neoadjuvant chemotherapy. Cancer Discov 5(8):821–831. Scholar
  6. 6.
    Cibulskis K, Lawrence MS, Carter SL, Sivachenko A, Jaffe D, Sougnez C et al (2013) Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat Biotechnol 31(3):213–219. Scholar
  7. 7.
    Koboldt DC, Zhang Q, Larson DE, Shen D, McLellan MD, Lin L et al (2012) VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res 22(3):568–576. Scholar
  8. 8.
    Favero F, Joshi T, Marquard AM, Birkbak NJ, Krzystanek M, Li Q et al (2015) Sequenza: allele-specific copy number and mutation profiles from tumor sequencing data. Ann Oncol 26(1):64–70. Scholar
  9. 9.
    Schwarz RF, Trinh A, Sipos B, Brenton JD, Goldman N, Markowetz F (2014) Phylogenetic quantification of intra-tumour heterogeneity. PLoS Comput Biol 10(4):e1003535. Scholar
  10. 10.
    Schliep KP (2011) phangorn: phylogenetic analysis in R. Bioinformatics 27(4):592–593. Scholar
  11. 11.
    Rosenthal R, McGranahan N, Herrero J, Taylor BS, Swanton C (2016) deconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution. Genome Biol 17(1):31. Scholar
  12. 12.
    Roth A, Khattra J, Yap D, Wan A, Laks E, Biele J et al (2014) PyClone: statistical inference of clonal population structure in cancer. Nat Methods 11(4):396–398. Scholar
  13. 13.
    Miller CA, White BS, Dees ND, Griffith M, Welch JS, Griffith OL et al (2014) SciClone: inferring clonal architecture and tracking the spatial and temporal patterns of tumor evolution. PLoS Comput Biol 10(8):e1003665. Scholar
  14. 14.
    McGranahan N, Favero F, de Bruin EC, Birkbak NJ, Szallasi Z, Swanton C (2015) Clonal status of actionable driver events and the timing of mutational processes in cancer evolution. Sci Transl Med 7(283):283ra54. Scholar
  15. 15.
    Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV et al (2013) Signatures of mutational processes in human cancer. Nature 500(7463):415–421. Scholar
  16. 16.
    Qiao Y, Quinlan AR, Jazaeri AA, Verhaak RG, Wheeler DA, Marth GT (2014) SubcloneSeeker: a computational framework for reconstructing tumor clone structure for cancer variant interpretation and prioritization. Genome Biol 15(8):443. Scholar
  17. 17.
    Yuan K, Sakoparnig T, Markowetz F, Beerenwinkel N (2015) BitPhylogeny: a probabilistic framework for reconstructing intra-tumor phylogenies. Genome Biol 16:36. Scholar
  18. 18.
    Deshwar AG, Vembu S, Yung CK, Jang GH, Stein L, Morris Q (2015) PhyloWGS: reconstructing subclonal composition and evolution from whole-genome sequencing of tumors. Genome Biol 16:35. Scholar
  19. 19.
    Popic V, Salari R, Hajirasouliha I, Kashef-Haghighi D, West RB, Batzoglou S (2015) Fast and scalable inference of multi-sample cancer lineages. Genome Biol 16:91. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Gerald Goh
    • 1
    • 2
    Email author
  • Nicholas McGranahan
    • 1
  • Gareth A. Wilson
    • 3
    • 4
  1. 1.Cancer Research UK Lung Cancer Centre of ExcellenceUniversity College London Cancer InstituteLondonUK
  2. 2.Genome Institute of SingaporeSingaporeSingapore
  3. 3.Cancer Research UK Lung Cancer Centre of ExcellenceUniversity College London Cancer InstituteLondonUK
  4. 4.Translational Cancer Therapeutics LaboratoryThe Francis Crick InstituteLondonUK

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