Identification of the mutation signature of the cancer genome caused by irradiation
Identification of the mutation signature of the cancer genome caused by irradiation
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DOI：
10.1016/j.radonc.2020.10.020
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发表时间：
2021-02-01
影响因子：
5.7
通讯作者：
Akimoto, Tetsuo
中科院分区：
文献类型：
--
作者：
Kageyama, Shun-Ichiro;Du, Junyan;Akimoto, Tetsuo
背景和目的：电离辐射可导致肿瘤细胞基因组突变，并作为一种有效的癌症治疗方法。然而，电离辐射后的癌症基因组中的突变签名还没有被documented.Materials和方法：我们建立了一个体外实验系统来分析辐射（60戈伊/20 Fr/4周）食管癌细胞系的癌症基因组中的从头突变的存在。随后，我们进行了全基因组，染色质免疫沉淀，RNA测序使用未经处理的和辐照的样品，以评估辐射引起的基因组损伤，并了解潜在的mechanism.Results：辐照的癌细胞表现出热点的从头8502-12966单核苷酸变异和954- 1331插入缺失的染色体上。这些单核苷酸变异主要来源于双链断裂修复错误，如使用突变特征分析所确定的。热点部分重叠的网站H3 K9三甲基化，这是一个弱的双链断裂repair.Conclusion能力的区域，其特征在于：本研究突出了癌症基因组的辐射的签名和潜在的机制。(C)2020作者由爱思唯尔公司出版
Background and purpose: Ionising radiation causes mutations in the genomes of tumour cells and serves as a potent treatment for cancer. However, the mutation signatures in the cancer genome following ionising radiation have not been documented.Materials and methods: We established an in vitro experimental system to analyse the presence of de novo mutations in the cancer genome of irradiated (60 Gy/20 fr/4 weeks) oesophageal cancer cell lines. Subsequently, we performed whole-genome, chromatin immunoprecipitation, and RNA sequencing using untreated and irradiated samples to assess the damage to the genome caused by radiation and understand the underlying mechanism.Results: The irradiated cancer cells exhibited hotspots for the de novo 8502-12966 single nucleotide variants and 954-1,331 indels on the chromosome. These single nucleotide variants primarily originated from double-stranded break repair errors, as determined using mutation signature analysis. The hotspots partially overlapped with the sites of H3K9 trimethylation, which are regions characterised by a weak capacity for double-stranded break repair.Conclusion: This study highlights the signature and underlying mechanism of radiation on the cancer genome. (C) 2020 The Authors. Published by Elsevier B.V.