Nature communications · 2016
A genetic basis for the variation in the vulnerability of cancer to DNA damage.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Yard Brian D, Adams Drew J, Chie Eui Kyu, Tamayo Pablo, Battaglia Jessica S, Gopal Priyanka, Rogacki Kevin, Pearson Bradley E, Phillips James, Raymond Daniel P, Pennell Nathan A, Almeida Francisco, Cheah Jaime H, Clemons Paul A, Shamji Alykhan, Peacock Craig D, Schreiber Stuart L, Hammerman Peter S, Abazeed Mohamed E
Аннотация
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.