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Tp73 DeltaEx2 - 3亚型转录水平升高在低级别胶质瘤患者中的预后价值

Prognostic value of increase in transcript levels of Tp73 DeltaEx2-3 isoforms in low-grade glioma patients.

作者信息

Wager M, Guilhot J, Blanc J-L, Ferrand S, Milin S, Bataille B, Lapierre F, Denis S, Chantereau T, Larsen C-J, Karayan-Tapon L

机构信息

Neurosurgery Department, University Hospital, Poitiers, France.

出版信息

Br J Cancer. 2006 Oct 23;95(8):1062-9. doi: 10.1038/sj.bjc.6603410.

Abstract

Glial tumours are a devastating, poorly understood condition carrying a gloomy prognosis for which clinicians sorely lack reliable predictive parameters facilitating a sound treatment strategy. Tp73, a p53 family member, expresses two main classes of isoforms--transactivatory activity (TA)p73 and DeltaTAp73--exhibiting tumour suppressor gene and oncogene properties, respectively. The authors examined their expression status in high- and low-grade adult gliomas. Isoform-specific real-time reverse transcription-polymerase chain reaction was used for the analysis of Tp73 isoform transcript expression in a series of 51 adult patients harbouring glial tumours, in order to compare tumour grades with each other, and with non-tumoural samples obtained from epileptic patients as well. Our data demonstrate increase of TAp73 and DeltaTAp73 transcript levels at onset and early stage of the disease. We also show that DeltaEx2-3 isoform expression in low-grade tumours anticipates clinical and imaging progression to higher grades, and correlates to the patients' survival. Expression levels of P1 promoter generated Tp73 isoforms--and particularly DeltaEx2-3--indeed allow for prediction of the clinical progression of low-grade gliomas in adults. Our data are the first such molecular biology report regarding low-grade tumours and as such should be of help for sound decision-making.

摘要

胶质肿瘤是一种严重且了解甚少的疾病,预后不佳,临床医生极度缺乏有助于制定合理治疗策略的可靠预测参数。Tp73是一种p53家族成员,表达两种主要类型的异构体——具有反式激活活性(TA)的p73和ΔTAp73,分别表现出肿瘤抑制基因和癌基因特性。作者检测了它们在成人高低级别胶质瘤中的表达状态。采用异构体特异性实时逆转录-聚合酶链反应,分析了51例患有胶质肿瘤的成年患者系列样本中Tp73异构体转录本的表达情况,以便相互比较肿瘤级别,并与从癫痫患者获得的非肿瘤样本进行比较。我们的数据表明,疾病发作和早期阶段TAp73和ΔTAp73转录水平升高。我们还表明,低级别肿瘤中ΔEx2-3异构体的表达预示着临床和影像学进展为更高级别,并与患者的生存率相关。P1启动子产生的Tp73异构体——尤其是ΔEx2-3——的表达水平确实能够预测成人低级别胶质瘤的临床进展。我们的数据是关于低级别肿瘤的首份此类分子生物学报告,因此应有助于做出合理决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e714/2360700/c0b33c0a3c21/95-6603410f1.jpg

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