title: Molecular profiling reveals frequent gain of MYCN and anaplasia-specific loss of 4q and 14q in Wilms tumor.
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.
authors: Molecular Haematology and Cancer Biology Unit, University College London, Institute of Child Health, London, UK.
authors: Richard D
authors: RD
authors: Williams
authors: Reem
authors: R
authors: Al-Saadi
authors: Rachael
authors: R
authors: Natrajan
authors: Alan
authors: A
authors: Mackay
authors: Tasnim
authors: T
authors: Chagtai
authors: Suzanne
authors: S
authors: Little
authors: Sandra N
authors: SN
authors: Hing
authors: Kerry
authors: K
authors: Fenwick
authors: Alan
authors: A
authors: Ashworth
authors: Paul
authors: P
authors: Grundy
authors: James R
authors: JR
authors: Anderson
authors: Jeffrey S
authors: JS
authors: Dome
authors: Elizabeth J
authors: EJ
authors: Perlman
authors: Chris
authors: C
authors: Jones
authors: Kathy
authors: K
authors: Pritchard-Jones
mesh_terms: D000293:Adolescent; D000708:Anaplasia / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002883:Chromosomes, Human, Pair 14; D002894:Chromosomes, Human, Pair 4; D055028:Comparative Genomic Hybridization / Q000379:methods; D056915:DNA Copy Number Variations; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D000071447:N-Myc Proto-Oncogene Protein; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D015513:Oncogene Proteins / Q000235:genetics*; D016019:Survival Analysis; D009396:Wilms Tumor / Q000235:genetics*
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins