Prognostic value of increase in transcript levels of Tp73 ΔEx2-3 isoforms in low-grade glioma patients

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 ΔTAp73 - 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 ΔTAp73 transcript levels at onset and early stage of the disease. We also show that ΔEx2-3 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 ΔEx2-3 - 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. © 2006 Cancer Research UK.