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

Research output: Contribution to journalArticle

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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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Chromosomes, Human, Pair 12
Wilms Tumor
Neoplasms
Genes
Survival
Gene Expression
Recurrence
Chromosome Aberrations
Down-Regulation
Databases
Mutation

ASJC Scopus subject areas

  • Cancer Research

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

In: Neoplasia (United States), Vol. 21, No. 1, 01.01.2019, p. 117-131.

Research output: Contribution to journalArticle

Haruta, M, Arai, Y, Okita, H, Tanaka, Y, Takimoto, T, Sugino, RP, 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), vol. 21, no. 1, pp. 117-131. https://doi.org/10.1016/j.neo.2018.10.007
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. / Combined Genetic and Chromosomal Characterization of Wilms Tumors Identifies Chromosome 12 Gain as a Potential New Marker Predicting a Favorable Outcome. In: Neoplasia (United States). 2019 ; Vol. 21, No. 1. pp. 117-131.
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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.",
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