1. Combined Genetic and Chromosomal Characterization of Wilms Tumors Identifies Chromosome 12 Gain as a Potential New Marker Predicting a Favorable Outcome
- Author
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Yasuhiko Kaneko, Takehiko Kamijo, Tsugumichi Koshinaga, Yukichi Tanaka, Masahiro Fukuzawa, Masayuki Haruta, Takaharu Oue, Yasuhito Arai, Tetsuya Takimoto, Ryuichi P. Sugino, Yasuhiro Yamada, and Hajime Okita
- Subjects
0301 basic medicine ,Male ,Cancer Research ,0302 clinical medicine ,Risk groups ,Gene expression ,Chromosome Duplication ,Favorable outcome ,Child ,Comparative Genomic Hybridization ,aCGH, array comparative genomic hybridization ,Prognosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030220 oncology & carcinogenesis ,Child, Preschool ,Female ,ROI, retention of imprinting ,TSG, tumor suppressor gene ,Original article ,Adolescent ,DNA Copy Number Variations ,Genotype ,Biology ,Polymorphism, Single Nucleotide ,Wilms Tumor ,lcsh:RC254-282 ,OS, overall survival ,03 medical and health sciences ,RFS, relapse-free survival ,miRNAPG, microRNA processing gene ,Overall survival ,Biomarkers, Tumor ,Humans ,LOI, loss of imprinting ,LOH, loss of heterozygosity ,Gene ,Chromosome 12 ,Neoplasm Staging ,Chromosome Aberrations ,UPD, uniparental disomy ,Chromosomes, Human, Pair 12 ,Gene Expression Profiling ,Chromosome ,Infant ,WT, Wilms tumor ,Survival Analysis ,030104 developmental biology ,Mutation ,Cancer research ,Intermediate risk - 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.
- Published
- 2019