Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients.
Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients.
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DOI：
10.1186/1471-2350-11-123
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发表时间：
2010-08-11
影响因子：
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通讯作者：
Imai T
中科院分区：
文献类型：
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作者：
Michikawa Y;Suga T;Ishikawa A;Hayashi H;Oka A;Inoko H;Iwakawa M;Imai T
接受放射治疗的癌症患者的正常组织的反应各不相同，可能是由于遗传差异引起的放射敏感性变化。癌症患者（n = 360）从RadGenomics项目中回顾性选择。使用美国国家癌症研究所通用毒性标准对放疗完成3个月内的不良反应进行分级;高级别组为3级或以上（n = 180），低级别组为1级或以下（n = 180）。使用23，244个微卫星筛选合并的基因组DNA（gDNA）（每组n = 90）。使用剩余的合并gDNA分析具有不同组间频率的标志物（Fisher精确检验P < 0.05）。在培养的正常人皮肤成纤维细胞中进行沉默RNA处理。47个标记具有正关联值;包括SEMA 3A启动子区的1个（P = 1.24 × 10-5）。SEMA 3A敲低增强了辐射抗性。这项研究确定了47个假定的放射敏感性标志物，并提出了SEMA 3A在放射敏感性中的作用。
The response of normal tissues in cancer patients undergoing radiotherapy varies, possibly due to genetic differences underlying variation in radiosensitivity. Cancer patients (n = 360) were selected retrospectively from the RadGenomics project. Adverse effects within 3 months of radiotherapy completion were graded using the National Cancer Institute Common Toxicity Criteria; high grade group were grade 3 or more (n = 180), low grade group were grade 1 or less (n = 180). Pooled genomic DNA (gDNA) (n = 90 from each group) was screened using 23,244 microsatellites. Markers with different inter-group frequencies (Fisher exact test P < 0.05) were analyzed using the remaining pooled gDNA. Silencing RNA treatment was performed in cultured normal human skin fibroblasts. Forty-seven markers had positive association values; including one in the SEMA3A promoter region (P = 1.24 × 10-5). SEMA3A knockdown enhanced radiation resistance. This study identified 47 putative radiosensitivity markers, and suggested a role for SEMA3A in radiosensitivity.