Introduction

Identification of somatic rearrangements in cancer genomes has accelerated through analysis of high-throughput sequencing data. However, characterization of complex structural alterations and their underlying mechanisms remains inadequate. Here, applying an algorithm to predict structural variations from short reads, we report a comprehensive catalog of somatic structural variations and the mechanisms generating them, using high-coverage whole-genome sequencing data from 140 patients across ten tumor types. We characterize the relative contributions of different types of rearrangements and their mutational mechanisms, find that ~20% of the somatic deletions are complex deletions formed by replication errors, and describe the differences between the mutational mechanisms in somatic and germline alterations. Importantly, we provide detailed reconstructions of the events responsible for loss of CDKN2A/B and gain of EGFR in glioblastoma, revealing that these alterations can result from multiple mechanisms even in a single genome and that both DNA double-strand breaks and replication errors drive somatic rearrangements.

Publications

  1. Diverse mechanisms of somatic structural variations in human cancer genomes.
    Cite this
    Yang L, Luquette LJ, Gehlenborg N, Xi R, Haseley PS, Hsieh CH, Zhang C, Ren X, Protopopov A, Chin L, Kucherlapati R, Lee C, Park PJ, 2013-05-01 - Cell

Credits

  1. Lixing Yang
    Developer

    Center for Biomedical Informatics, Harvard Medical School, Morocco

  2. Lovelace J Luquette
    Developer

  3. Nils Gehlenborg
    Developer

  4. Ruibin Xi
    Developer

  5. Psalm S Haseley
    Developer

  6. Chih-Heng Hsieh
    Developer

  7. Chengsheng Zhang
    Developer

  8. Xiaojia Ren
    Developer

  9. Alexei Protopopov
    Developer

  10. Lynda Chin
    Developer

  11. Raju Kucherlapati
    Developer

  12. Charles Lee
    Developer

  13. Peter J Park
    Investigator

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Summary
AccessionBT000347
Tool TypeApplication
Category
PlatformsLinux/Unix
Technologies
User InterfaceTerminal Command Line
Download Count0
Submitted ByPeter J Park