Introduction

We describe a computational method that infers tumor purity and malignant cell ploidy directly from analysis of somatic DNA alterations. The method, named ABSOLUTE, can detect subclonal heterogeneity and somatic homozygosity, and it can calculate statistical sensitivity for detection of specific aberrations. We used ABSOLUTE to analyze exome sequencing data from 214 ovarian carcinoma tumor-normal pairs. This analysis identified both pervasive subclonal somatic point-mutations and a small subset of predominantly clonal and homozygous mutations, which were overrepresented in the tumor suppressor genes TP53 and NF1 and in a candidate tumor suppressor gene CDK12. We also used ABSOLUTE to infer absolute allelic copy-number profiles from 3,155 diverse cancer specimens, revealing that genome-doubling events are common in human cancer, likely occur in cells that are already aneuploid, and influence pathways of tumor progression (for example, with recessive inactivation of NF1 being less common after genome doubling). ABSOLUTE will facilitate the design of clinical sequencing studies and studies of cancer genome evolution and intra-tumor heterogeneity.

Publications

  1. Absolute quantification of somatic DNA alterations in human cancer.
    Cite this
    Carter SL, Cibulskis K, Helman E, McKenna A, Shen H, Zack T, Laird PW, Onofrio RC, Winckler W, Weir BA, Beroukhim R, Pellman D, Levine DA, Lander ES, Meyerson M, Getz G, 2012-05-01 - Nature biotechnology

Credits

  1. Scott L Carter
    Developer

    The Broad Institute of Harvard and MIT, Cambridge, United States of America

  2. Kristian Cibulskis
    Developer

  3. Elena Helman
    Developer

  4. Aaron McKenna
    Developer

  5. Hui Shen
    Developer

  6. Travis Zack
    Developer

  7. Peter W Laird
    Developer

  8. Robert C Onofrio
    Developer

  9. Wendy Winckler
    Developer

  10. Barbara A Weir
    Developer

  11. Rameen Beroukhim
    Developer

  12. David Pellman
    Developer

  13. Douglas A Levine
    Developer

  14. Eric S Lander
    Developer

  15. Matthew Meyerson
    Developer

  16. Gad Getz
    Investigator

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Summary
AccessionBT002367
Tool TypeApplication
Category
PlatformsLinux/Unix
TechnologiesR
User InterfaceTerminal Command Line
Download Count0
Submitted ByGad Getz