Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment.
Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment.
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DOI：
10.1038/sj.bjc.6604381
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发表时间：
2008-06-03
影响因子：
8.8
通讯作者：
Bouffler, S.
中科院分区：
文献类型：
--
作者：
Badie, C.;Dziwura, S.;Raffy, C.;Tsigani, T.;Alsbeih, G.;Moody, J.;Finnon, P.;Levine, E.;Scott, D.;Bouffler, S.
关键词：
放射治疗的正常组织反应在患者中的严重程度不同，并且无法准确预测，从而限制了治疗剂量。遗传性放射敏感性综合征的存在表明，正常组织反应的严重程度是由遗传因素决定的，至少部分是由遗传因素决定的，这些因素可以通过基因表达的差异来揭示。为了检验这一假设，来自22名具有轻微（11）或非常严重的急性皮肤反应（11）的乳腺癌患者的外周血淋巴细胞培养物已被用于分析基因表达。在放疗前两组患者建立的T细胞培养物中，通过定量实时PCR测定四种辐射应答基因（CDKN1A、GADD45A、CCNB1和BBC3）的基础和照射后表达。2戈伊X射线照射后2小时，BBC3、CCNB1和GADD 45 A的相对表达水平在组间没有区别。然而，与正常人相比，严重反应者中照射后CDKN1A的表达反应显著降低（P<0.002）。使用该终点，可预测91%的采样个体的反应严重程度。TP53 Arg72 Pro和CDKN1A Ser31 Arg单核苷酸多态性分析未显示与反应敏感性有任何显著相关性。虽然这些结果需要确认和扩展，这项研究表明，在简单的测试预测急性皮肤辐射毒性的严重程度的可能性。
Normal tissue reactions to radiation therapy vary in severity among patients and cannot be accurately predicted, limiting treatment doses. The existence of heritable radiosensitivity syndromes suggests that normal tissue reaction severity is determined, at least in part, by genetic factors and these may be revealed by differences in gene expression. To test this hypothesis, peripheral blood lymphocyte cultures from 22 breast cancer patients with either minimal (11) or very severe acute skin reactions (11) have been used to analyse gene expression. Basal and post-irradiation expression of four radiation-responsive genes (CDKN1A, GADD45A, CCNB1, and BBC3) was determined by quantitative real-time PCR in T-cell cultures established from the two patient groups before radiotherapy. Relative expression levels of BBC3, CCNB1, and GADD45A 2 h following 2 Gy X-rays did not discriminate between groups. However, post-irradiation expression response was significantly reduced for CDKN1A (P<0.002) in severe reactors compared to normal. Prediction of reaction severity of ∼91% of individuals sampled was achieved using this end point. Analysis of TP53 Arg72Pro and CDKN1A Ser31Arg single nucleotide polymorphisms did not show any significant association with reaction sensitivity. Although these results require confirmation and extension, this study demonstrates the possibility of predicting the severity of acute skin radiation toxicity in simple tests.
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DOI：
10.1016/0360-3016(95)00068-a
发表时间：
1995-07-30
影响因子：
7
作者：
BROCK, WA;TUCKER, SL;PETERS, LJ
通讯作者：
PETERS, LJ
影响因子：
4.7
作者：
Li, GJ;Liu, ZS;Wei, QY
通讯作者：
Wei, QY
影响因子：
5.3
作者：
Badie, C;Itzhaki, JE;Porter, ACG
通讯作者：
Porter, ACG
影响因子：
5.7
作者：
Rodningen, Aug Kristin;Borresen-Dale, Anne-Lise;Overgaard, Jens
通讯作者：
Overgaard, Jens
影响因子：
56.9
作者：
Lee, JH;Paull, TT
通讯作者：
Paull, TT