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

• Published in: Neoplasia (New York, N.Y.) N.Y.), 2019-01, Vol.21 (1), p.117-131
• Main Authors: Haruta, Masayuki, Arai, Yasuhito, Okita, Hajime, Tanaka, Yukichi, Takimoto, Tetsuya, Sugino, Ryuichi P., Yamada, Yasuhiro, Kamijo, Takehiko, Oue, Takaharu, Fukuzawa, Masahiro, Koshinaga, Tsugumichi, Kaneko, Yasuhiko
• Format: Article
• Language: English
• Subjects: Adolescent; Biomarkers, Tumor; Child; Child, Preschool; Chromosome 12; Chromosome 16; Chromosome Aberrations; Chromosome Duplication; Chromosomes; Chromosomes, Human, Pair 12; Comparative Genomic Hybridization; DNA Copy Number Variations; Female; Gene expression; Gene Expression Profiling; Genotype; Humans; Infant; Male; Medical prognosis; Mutation; Neoplasm Staging; Polymorphism, Single Nucleotide; Prognosis; Risk groups; Survival; Survival Analysis; Tumors; Wilms Tumor - diagnosis; Wilms Tumor - genetics; Wilms Tumor - mortality
• ISSN: 1476-5586; 1522-8002; 1476-5586
• DOI: 10.1016/j.neo.2018.10.007

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.