Combined Genetic and Chromosomal Characterization of Wilms Tumors Identifies Chromosome 12 Gain as a Potential New Marker Predicting a Favorable Outcome
Combined Genetic and Chromosomal Characterization of Wilms Tumors Identifies Chromosome 12 Gain as a Potential New Marker Predicting a Favorable Outcome
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DOI：
10.1016/j.neo.2018.10.007
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发表时间：
2019-01-01
期刊：
影响因子：
4.8
通讯作者：
Kaneko, Yasuhiko
中科院分区：
文献类型：
--
作者：
Haruta, Masayuki;Arai, Yasuhito;Kaneko, Yasuhiko
为了确定预后因素，阵列CGH（aCGH）模式和突变的WT 1和其他9个基因进行了分析，在128个单侧肾母细胞瘤（WT）。20名患者无aCGH畸变，31名患者有WT 1改变[沉默型和WT 1型：无复发生存率（RFS）分别为95%和83%]。77例aCGH改变而无WT 1改变（非沉默/非WT 1型），并分为+ 12、11 q-、16 q-或HACE 1缺失或无缺失的患者。有+ 12缺失的患者RFS优于无+ 12缺失的患者（P = 0.010），有+11 q-、16 q-或HACE 1缺失的患者RFS低于无+11 q-、16 q-或HACE 1缺失的患者（分别为P = 0.001、0.025或1.2E-04）。将无症状型和WT 1型以及8种亚型肿瘤整合并分为3个风险组：无症状型和+ 12亚组为低风险;无+ 12加11 q-、16 q-或MACE 1缺失亚组为高风险; WT 1型和无+ 12加无11 q-、16 q-或MACE 1缺失亚组为中等风险。在检测的27例WT中，12号染色体上146个基因在+12肿瘤中的表达强于非+ 12肿瘤，而16号染色体上10个基因在16号染色体肿瘤中的表达弱于非16号染色体肿瘤。基于公共数据库，146个上调基因中有75个的过表达和10个下调基因中有7个的低表达分别与更好和更差的总生存率相关。+ 12被鉴定为预测有利结果的潜在新标记，染色体异常可能与这些异常相关的基因表达改变有关。
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 27WTsexamined, the expression of 146 genes on chromosome 12was stronger in+ 12tumors than in no+ 12 tumors, while that of 10 genes on 16q wasweaker 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 abnormalitiesmay be related to altered gene expression associated with these abnormalities.