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A genetic basis for the variation in the vulnerability of cancer to DNA damage

Author

Listed:
  • Brian D. Yard

    (Cleveland Clinic)

  • Drew J. Adams

    (Case Western Reserve University)

  • Eui Kyu Chie

    (Cleveland Clinic
    Seoul National University College of Medicine)

  • Pablo Tamayo

    (Broad Institute of MIT and Harvard)

  • Jessica S. Battaglia

    (Cleveland Clinic)

  • Priyanka Gopal

    (Cleveland Clinic)

  • Kevin Rogacki

    (Cleveland Clinic)

  • Bradley E. Pearson

    (Dana-Farber Cancer Institute)

  • James Phillips

    (Cleveland Clinic)

  • Daniel P. Raymond

    (Cleveland Clinic)

  • Nathan A. Pennell

    (Cleveland Clinic)

  • Francisco Almeida

    (Cleveland Clinic)

  • Jaime H. Cheah

    (Broad Institute of MIT and Harvard
    Center for the Science of Therapeutics, Broad Institute)

  • Paul A. Clemons

    (Broad Institute of MIT and Harvard
    Center for the Science of Therapeutics, Broad Institute)

  • Alykhan Shamji

    (Broad Institute of MIT and Harvard
    Center for the Science of Therapeutics, Broad Institute)

  • Craig D. Peacock

    (Cleveland Clinic)

  • Stuart L. Schreiber

    (Broad Institute of MIT and Harvard
    Center for the Science of Therapeutics, Broad Institute
    Harvard University
    Howard Hughes Medical Institute, Broad Institute)

  • Peter S. Hammerman

    (Broad Institute of MIT and Harvard
    Dana-Farber Cancer Institute)

  • Mohamed E. Abazeed

    (Cleveland Clinic
    Cleveland Clinic)

Abstract

Radiotherapy is not currently informed by the genetic composition of an individual patient’s tumour. To identify genetic features regulating survival after DNA damage, here we conduct large-scale profiling of cellular survival after exposure to radiation in a diverse collection of 533 genetically annotated human tumour cell lines. We show that sensitivity to radiation is characterized by significant variation across and within lineages. We combine results from our platform with genomic features to identify parameters that predict radiation sensitivity. We identify somatic copy number alterations, gene mutations and the basal expression of individual genes and gene sets that correlate with the radiation survival, revealing new insights into the genetic basis of tumour cellular response to DNA damage. These results demonstrate the diversity of tumour cellular response to ionizing radiation and establish multiple lines of evidence that new genetic features regulating cellular response after DNA damage can be identified.

Suggested Citation

  • Brian D. Yard & Drew J. Adams & Eui Kyu Chie & Pablo Tamayo & Jessica S. Battaglia & Priyanka Gopal & Kevin Rogacki & Bradley E. Pearson & James Phillips & Daniel P. Raymond & Nathan A. Pennell & Fran, 2016. "A genetic basis for the variation in the vulnerability of cancer to DNA damage," Nature Communications, Nature, vol. 7(1), pages 1-14, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11428
    DOI: 10.1038/ncomms11428
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