Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors.
Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors.
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DOI：
10.1016/j.ccell.2015.01.003
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发表时间：
2015-02-09
期刊：
影响因子：
50.3
通讯作者：
Perlman EJ
中科院分区：
文献类型：
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作者：
Walz AL;Ooms A;Gadd S;Gerhard DS;Smith MA;Guidry Auvil JM;Meerzaman D;Chen QR;Hsu CH;Yan C;Nguyen C;Hu Y;Bowlby R;Brooks D;Ma Y;Mungall AJ;Moore RA;Schein J;Marra MA;Huff V;Dome JS;Chi YY;Mullighan CG;Ma J;Wheeler DA;Hampton OA;Jafari N;Ross N;Gastier-Foster JM;Perlman EJ
我们报告了有利组织学肾母细胞瘤 (FHWT) 中最常见的单核苷酸取代/缺失突变发生在 SIX1/2（534 个肿瘤中的 7%）和 microRNA 处理基因 (miRNAPG) DGCR8 和 DROSHA（534 个肿瘤中的 15%）内。对 77 个 FHWT 的综合分析表明，具有 SIX1/2 和/或 miRNAPG 突变的肿瘤表现出诱导前后肾间质基因表达模式，并且与叶周肾源性休息和 11p15 印记畸变显着相关。 miRNAPG 突变肿瘤中成熟 Let-7a 和 miR-200 家族（负责间充质到上皮细胞转变）的表达显着降低，与未分化的胚芽组织学相关。同一肿瘤中的 6 种突变和 miRNAPG 突变的组合与 RAS 激活以及较高的复发率和死亡率相关。
We report the most common single nucleotide substitution/deletion mutations in Favorable Histology Wilms Tumors (FHWT) to occur within SIX1/2 (7% of 534 tumors) and microRNA processing genes (miRNAPG) DGCR8 and DROSHA (15% of 534 tumors). Comprehensive analysis of 77 FHWTs indicates that tumors with SIX1/2 and/or miRNAPG mutations show a pre-induction metanephric mesenchyme gene expression pattern and are significantly associated with both perilobar nephrogenic rests and 11p15 imprinting aberrations. Significantly decreased expression of mature Let-7a and the miR-200 family (responsible for mesenchymal-to-epithelial transition) in miRNAPG-mutant tumors is associated with an undifferentiated blastemal histology. The combination of SIX and miRNAPG mutations in the same tumor is associated with evidence of RAS activation and a higher rate of relapse and death.