Molecular profiling reveals frequent gain of MYCN and anaplasia-specific loss of 4q and 14q in wilms tumor
Article first published online: 31 AUG 2011
Copyright © 2011 Wiley Periodicals, Inc.
Genes, Chromosomes and Cancer
Volume 50, Issue 12, pages 982–995, December 2011
How to Cite
Williams, R. D., Al-Saadi, R., Natrajan, R., Mackay, A., Chagtai, T., Little, S., Hing, S. N., Fenwick, K., Ashworth, A., Grundy, P., Anderson, J. R., Dome, J. S., Perlman, E. J., Jones, C. and Pritchard-Jones, K. (2011), Molecular profiling reveals frequent gain of MYCN and anaplasia-specific loss of 4q and 14q in wilms tumor. Genes Chromosom. Cancer, 50: 982–995. doi: 10.1002/gcc.20907
- Issue published online: 10 OCT 2011
- Article first published online: 31 AUG 2011
- Manuscript Accepted: 22 JUN 2011
- Manuscript Received: 22 DEC 2010
- Cancer Research UK. Grant Numbers: C1188/A11859, C1188/A4614
- Royal Marsden Hospital
Anaplasia in Wilms tumor, a distinctive histology characterized by abnormal mitoses, is associated with poor patient outcome. While anaplastic tumors frequently harbour TP53 mutations, little is otherwise known about their molecular biology. We have used array comparative genomic hybridization (aCGH) and cDNA microarray expression profiling to compare anaplastic and favorable histology Wilms tumors to determine their common and differentiating features. In addition to changes on 17p, consistent with TP53 deletion, recurrent anaplasia-specific genomic loss and under-expression were noted in several other regions, most strikingly 4q and 14q. Further aberrations, including gain of 1q and loss of 16q were common to both histologies. Focal gain of MYCN, initially detected by high resolution aCGH profiling in 6/61 anaplastic samples, was confirmed in a significant proportion of both tumor types by a genomic quantitative PCR survey of over 400 tumors. Overall, these results are consistent with a model where anaplasia, rather than forming an entirely distinct molecular entity, arises from the general continuum of Wilms tumor by the acquisition of additional genomic changes at multiple loci. © 2011 Wiley Periodicals, Inc.