Article
Expression analysis of 41 genes identifies a number of novel prognostic markers in Wilms tumors
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Published: | March 20, 2006 |
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Wilms tumors arise in one of 10,000 life births with the highest incidence before the age of five, which make them the most common malignant kidney tumor in childhood. Although current treatment protocols achieve cure rates of about 90%, balancing the side-effects of therapy against relapse risk remains challenging. Therefore, new prognostic markers could help to select the optimal amount of therapy for each patient and thus reduce side effects without increasing the risk for later relapse. On the other hand this may help to identify those children that would benefit from even more aggressive therapeutic strategies. Since numerous studies correlated expression differences of individual genes with higher relapse risk or death rate in Wilms tumors in the last years, we reinvestigated those genes with quantitative RT-PCR in a large set of 130 Wilms tumors. Comparing data from our much larger series of tumors with those from prior investigations, we could substantiate only some of the previously reported associations. In our series of 130 tumors and 41 genes we found significant expression differences for several clinical parameters, most notably relapse and death. ABCC1, BCL2, CD44_v5, HEY2 and TRIM22 were downregulated, whereas ID4, MYCN, TERT as well as TOP2a were upregulated in tumors that later relapsed. Similarly, HEY2 and TRIM22 were downregulated and ID4 and MYCN were upregulated in tumors with fatal outcome. Interestingly, expression differences of HEY2 and TRIM22 were always highly significant (p-value << 0.01). Our results identify a set of genes that may facilitate further classification of Wilms tumors and improve prediction of outcome to adjust subsequent treatment.