小柯机器人

美国杰克逊基因医学实验室Roel G. W. Verhaak、Floris P. Barthel等研究人员合作发现，放射治疗与导致癌症患者预后不良的缺失特征相关。2021年5月27日《自然—遗传学》杂志在线发表了这项成果。

研究人员分析了来自神经胶质瘤纵向分析联盟的190对原发性和复发性神经胶质瘤以及来自Hartwig医学基金会的3,693例治疗后转移性肿瘤的放射治疗后的突变谱。结果表明，与放射疗法相关的小片段缺失（5–15 bp）和大片段缺失（20+bp至染色体臂长度）的负担显著增加。与非照射肿瘤中预先存在的缺失和缺失相比，小缺失的特点是跨度较大，缺乏断点微同源性，并且在基因组上更分散。

突变特征分析涉及放疗后经典的非同源末端连接介导的DNA损伤修复和APOBEC突变。高辐射相关缺失负担与较差的临床结果相关，这表明有效修复辐射诱导的DNA损伤不利于患者的生存。这些结果可用于预测复发性癌症对放射治疗的敏感性。

据悉，电离辐射会导致 DNA 损伤，并且是癌症治疗的支柱，但对其基因组影响的了解有限。

附：英文原文

Title: Radiotherapy is associated with a deletion signature that contributes to poor outcomes in patients with cancer

Author: Emre Kocakavuk, Kevin J. Anderson, Frederick S. Varn, Kevin C. Johnson, Samirkumar B. Amin, Erik. P. Sulman, Martijn P. Lolkema, Floris P. Barthel, Roel G. W. Verhaak

Issue&Volume: 2021-05-27

Abstract: Ionizing radiation causes DNA damage and is a mainstay for cancer treatment, but understanding of its genomic impact is limited. We analyzed mutational spectra following radiotherapy in 190 paired primary and recurrent gliomas from the Glioma Longitudinal Analysis Consortium and 3,693 post-treatment metastatic tumors from the Hartwig Medical Foundation. We identified radiotherapy-associated significant increases in the burden of small deletions (5–15 bp) and large deletions (20+bp to chromosome-arm length). Small deletions were characterized by a larger span size, lacking breakpoint microhomology and were genomically more dispersed when compared to pre-existing deletions and deletions in non-irradiated tumors. Mutational signature analysis implicated classical non-homologous end-joining-mediated DNA damage repair and APOBEC mutagenesis following radiotherapy. A high radiation-associated deletion burden was associated with worse clinical outcomes, suggesting that effective repair of radiation-induced DNA damage is detrimental to patient survival. These results may be leveraged to predict sensitivity to radiation therapy in recurrent cancer.

DOI: 10.1038/s41588-021-00874-3

Source: https://www.nature.com/articles/s41588-021-00874-3

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex