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  • [Nat Commun] A genetic basis for the variation in the vulnerability of cancer to DNA damage.

    Cleveland Clinic / Mohamed E. Abazeed*

  • 출처
    Nat Commun
  • 등재일
    2016 Apr 25
  • 저널이슈번호
    7:11428. doi: 10.1038/ncomms11428.
  • 내용

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    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. 

     

    Author information

    Yard BD1, Adams DJ2, Chie EK1,3, Tamayo P4, Battaglia JS1, Gopal P1, Rogacki K1, Pearson BE5, Phillips J1, Raymond DP6, Pennell NA7, Almeida F8, Cheah JH4,9, Clemons PA4,9, Shamji A4,9, Peacock CD1, Schreiber SL4,9,10,11, Hammerman PS4,5, Abazeed ME1,12.

    1Department of Translational Hematology Oncology Research, Cleveland Clinic, 9500 Euclid Avenue/R40, Cleveland, Ohio 44195, USA.

    2Department of Genetics, Case Western Reserve University, 2109 Adelbert Road/BRB, Cleveland, Ohio 44106, USA.

    3Department of Radiation Oncology, Seoul National University College of Medicine, 101, Daehak-Ro, Jongno-Gu, Seoul 110-774, Korea.

    4Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA.

    5Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA.

    6Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, 9500 Euclid Avenue/J4-1, Cleveland, Ohio 44195, USA.

    7Department of Hematology and Medical Oncology, Cleveland Clinic, 9500 Euclid Avenue/R40, Cleveland, Ohio 44195, USA.

    8Department of Pulmonary Medicine, Cleveland Clinic, 9500 Euclid Avenue/M2-141, Cleveland, Ohio 44195, USA.

    9Center for the Science of Therapeutics, Broad Institute, 415 Main Street, Cambridge, Massachusetts 02142, USA.

    10Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.

    11Howard Hughes Medical Institute, Broad Institute, Cambridge, Massachusetts 02142, USA.

    12Department of Radiation Oncology, Cleveland Clinic, 9500 Euclid Avenue/T2, Cleveland, Ohio 44195, USA.

     

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