Molecular profiling reveals frequent gain of MYCN and anaplasia-specific loss of 4q and 14q in Wilms tumor

Richard D. Williams, Reem Al-Saadi, Rachael Natrajan, Alan Mackay, Tasnim Chagtai, Suzanne Little, Sandra N. Hing, Kerry Fenwick, Alan Ashworth, Paul Grundy, James R. Anderson, Jeffrey S. Dome, Elizabeth J. Perlman, Chris Jones, Kathy Pritchard-Jones*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)982-995
Number of pages14
JournalGenes Chromosomes and Cancer
Volume50
Issue number12
DOIs
StatePublished - Dec 2011

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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