Expression profiling of Wilms tumors reveals new candidate genes for different clinical parameters

• Published in: International journal of cancer Vol. 118; no. 8; pp. 1954 - 1962
• Main Authors: Zirn, B., Hartmann, O., Samans, B., Krause, M., Wittmann, S., Mertens, F., Graf, N., Eilers, M., Gessler, M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.04.2006; Wiley-Liss
• Subjects: Biological and medical sciences; Cancer and Oncology; Cancer och onkologi; Clinical Medicine; Disease Progression; E2F; Gene Expression Profiling; Humans; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Kidneys; Klinisk medicin; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; microarray; nephroblastoma; Nephrology. Urinary tract diseases; Oligonucleotide Array Sequence Analysis; Prognosis; retinoic acid; Reverse Transcriptase Polymerase Chain Reaction; Survival Analysis; Tretinoin - physiology; Tumors; Tumors of the urinary system; Wilms tumor; Wilms Tumor - genetics; Wilms Tumor - pathology; Kidney disease; Histological grading; Human; Urinary system disease; Prognosis; Retinoid; DNA chip; Malignant tumor; Metastasis; Gene expression; Gene expression profile; microarray; Cancerology; Histopathology; nephroblastoma; Transcription factor E2F; Wilms tumor; E2F; Genetics; Retinoic acid
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.21564

Wilms tumor is the most frequent renal neoplasm in children, but our understanding of its genetic basis is still limited. We performed cDNA microarray experiments using 63 primary Wilms tumors with the aim of detecting new candidate genes associated with malignancy grade and tumor progression. All tumors had received preoperative chemotherapy as mandated by the SIOP protocol, which sets this study apart from related approaches in the Unites States that are based on untreated samples. The stratification of expression data according to clinical criteria allowed a rather clear distinction between different subsets of Wilms tumors. Clear‐cut differences in expression patterns were discovered between relapse‐free as opposed to relapsed tumors and tumors with intermediate risk as opposed to high risk histology. Several differentially expressed genes, e.g.TRIM22, CENPF, MYCN, CTGF, RARRES3 and EZH2, were associated with Wilms tumor progression. For a subset of differentially expressed genes, microarray data were confirmed by real‐time RT‐PCR on the original set of tumors. Interestingly, we found the retinoic acid pathway to be deregulated at different levels in advanced tumors suggesting that treatment of these tumors with retinoic acid may represent a promising novel therapeutic approach. © 2005 Wiley‐Liss, Inc.