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

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, Francisco Almeida, Jaime H. Cheah, Paul A. Clemons, Alykhan Shamji, Craig D. Peacock, Stuart L. Schreiber, Peter S. Hammerman, Mohamed E. Abazeed*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

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.

Original languageEnglish (US)
Article number11428
JournalNature communications
Volume7
DOIs
StatePublished - Apr 25 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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