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.

中文翻译：

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癌症对DNA损伤的脆弱性变化的遗传基础。

放射治疗目前尚不了解个别患者肿瘤的遗传组成。为了确定调节DNA损伤后存活的遗传特征，在这里我们对533种经过遗传注释的人类肿瘤细胞系进行了大规模的细胞存活率分析。我们表明，对辐射的敏感性的特征是整个谱系之间和内部的显着变化。我们将平台的结果与基因组特征相结合，以识别可预测辐射敏感性的参数。我们确定体细胞拷贝数变化，基因突变和与辐射生存相关的单个基因和基因组的基础表达，揭示了肿瘤细胞对DNA损伤的遗传基础的新见解。