Combined Genetic and Chromosomal Characterization of Wilms Tumors Identifies Chromosome 12 Gain as a Potential New Marker Predicting a Favorable Outcome

Neoplasia. 2019 Jan;21(1):117-131. doi: 10.1016/j.neo.2018.10.007. Epub 2018 Dec 6.

Abstract

To identify prognostic factors, array CGH (aCGH) patterns and mutations in WT1 and 9 other genes were analyzed in 128 unilateral Wilms tumors (WTs). Twenty patients had no aCGH aberrations, and 31 had WT1 alterations [silent and WT1 types: relapse-free survival (RFS), 95% and 83%, respectively]. Seventy-seven patients had aCGH changes without WT1 alterations (nonsilent/non-WT1 type) and were subtyped into those with or without +12, 11q-, 16q-, or HACE1 loss. RFS was better for those with than those without +12 (P = .010) and worse for those with than those without 11q-, 16q-, or HACE1 loss (P = .001, .025, or 1.2E-04, respectively). Silent and WT1 type and 8 subtype tumors were integrated and classified into 3 risk groups: low risk for the silent type and +12 subgroup; high risk for the no +12 plus 11q-, 16q-, or HACE1 loss subgroup; intermediate risk for the WT1 type and no +12 plus no 11q-, 16q-, or HACE1 loss subgroup. Among the 27 WTs examined, the expression of 146 genes on chromosome 12 was stronger in +12 tumors than in no +12 tumors, while that of 10 genes on 16q was weaker in 16q- tumors than in no 16q- tumors. Overexpression in 75 out of 146 upregulated genes and underexpression in 7 out of 10 downregulated genes correlated with better and worse overall survival, respectively, based on the public database. +12 was identified as a potential new marker predicting a favorable outcome, and chromosome abnormalities may be related to altered gene expression associated with these abnormalities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers, Tumor*
  • Child
  • Child, Preschool
  • Chromosome Aberrations
  • Chromosome Duplication*
  • Chromosomes, Human, Pair 12*
  • Comparative Genomic Hybridization
  • DNA Copy Number Variations
  • Female
  • Gene Expression Profiling
  • Genotype
  • Humans
  • Infant
  • Male
  • Mutation
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Survival Analysis
  • Wilms Tumor / diagnosis
  • Wilms Tumor / genetics*
  • Wilms Tumor / mortality*

Substances

  • Biomarkers, Tumor