title: Bilateral wilms tumor with TP53-related anaplasia.
abstract: Wilms tumor (WT) with diffuse anaplasia has an unfavorable prognosis and is often (>70%) associated with mutations in the TP53 gene. Although most WTs are unilateral, 5-10% are bilateral, and they are almost always present with nephrogenic rests. The latter are considered a precursor of WT. Two cases of bilateral WTs with nephroblastomatosis, in which anaplastic changes were detected over a period of time, were analyzed using clinical, radiological, histopathological, and molecular-genetic data. TP53 was analyzed by direct sequencing of its full coding sequence and intron-exon boundaries in 11 fragments. DNA was extracted from paraffin-embedded or frozen specimens. High-resolution genomic copy number profiling was carried out by UCL Genomics on the Affymetrix Human Mapping 250K Nsp or Genome-Wide Human SNP Array 6.0 platform. Both cases demonstrated a strong association between the appearance of anaplastic clones and TP53 mutations. Synchronous ganglioneuroma was diagnosed in one case. Our cases are unique as they represent a long disease history and demonstrate the difficulties in managing rare cases of bilateral WT with anaplasia. These cases also emphasize the practical importance of modern molecular-genetic techniques and their clinical application. Moreover, they highlight the issue of the adequate sampling needed in order to gather comprehensive, efficient, and sufficient information about genetic events in a single tumor.
authors: Divisions of Molecular Pathology and Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, United Kingdom. sergey.popov@icr.ac.uk
authors: Sergey D
authors: SD
authors: Popov
authors: Gordan M
authors: GM
authors: Vujanic
authors: Neil J
authors: NJ
authors: Sebire
authors: Tasnim
authors: T
authors: Chagtai
authors: Richard
authors: R
authors: Williams
authors: Sucheta
authors: S
authors: Vaidya
authors: Kathy
authors: K
authors: Pritchard-Jones
mesh_terms: D000708:Anaplasia; D002675:Child, Preschool; D005260:Female; D018628:Gene Dosage; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D009396:Wilms Tumor / Q000235:genetics* / Q000473:pathology*