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

Masayuki Haruta, Yasuhito Arai, Hajime Okita, Yukichi Tanaka, Tetsuya Takimoto, Ryuichi P. Sugino, Yasuhiro Yamada, Takehiko Kamijo, Takaharu Oue, Masahiro Fukuzawa, Tsugumichi Koshinaga, Yasuhiko Kaneko

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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.

Original languageEnglish
Pages (from-to)117-131
Number of pages15
JournalNeoplasia (United States)
Volume21
Issue number1
DOIs
Publication statusPublished - 2019 Jan 1

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ASJC Scopus subject areas

  • Cancer Research

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Haruta, M., Arai, Y., Okita, H., Tanaka, Y., Takimoto, T., Sugino, R. P., Yamada, Y., Kamijo, T., Oue, T., Fukuzawa, M., Koshinaga, T., & Kaneko, Y. (2019). Combined Genetic and Chromosomal Characterization of Wilms Tumors Identifies Chromosome 12 Gain as a Potential New Marker Predicting a Favorable Outcome. Neoplasia (United States), 21(1), 117-131. https://doi.org/10.1016/j.neo.2018.10.007