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

Nat Commun
Authors
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.

Year of Publication
2016
Journal
Nat Commun
Volume
7
Pages
11428
Date Published
2016 Apr 25
ISSN
2041-1723
DOI
10.1038/ncomms11428
PubMed ID
27109210
PubMed Central ID
PMC4848553
Links
Grant list
K08 CA163677 / CA / NCI NIH HHS / United States
KL2 TR000440 / TR / NCATS NIH HHS / United States
P30 CA023100 / CA / NCI NIH HHS / United States
U01 CA176152 / CA / NCI NIH HHS / United States