Boublikova L, Bakardjieva-Mihaylova V, Skvarova Kramarzova K, Kuzilkova D, Dobiasova A, Fiser K, Stuchly J, Kotrova M, Buchler T, Dusek P, Grega M, Rosova B, Vernerova Z, Klezl P, Pesl M, Zachoval R, Krolupper M, Kubecova M, Stahalova V, Abrahamova J, Babjuk M, Kodet R, Trka J
Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
Cancer Lett. 2016 Jul 1;376(2):367-76. doi: 10.1016/j.canlet.2016.04.016. Epub 2016 Apr 13.
Wilms tumor gene 1 (WT1), a zinc-finger transcription factor essential for testis development and function, along with other genes, was investigated for their role in the pathogenesis of testicular germ cell tumors (TGCT).
In total, 284 TGCT and 100 control samples were investigated, including qPCR for WT1 expression and BRAF mutation, p53 immunohistochemistry detection, and massively parallel amplicon sequencing.
WT1 was significantly (p < 0.0001) under-expressed in TGCT, with an increased ratio of exon 5-lacking isoforms, reaching low levels in chemo-naïve relapsed TGCT patients vs. high levels in chemotherapy-pretreated relapsed patients. BRAF V600E mutation was identified in 1% of patients only. p53 protein was lowly expressed in TGCT metastases compared to the matched primary tumors. Of 9 selected TGCT-linked genes, RAS/BRAF and WT1 mutations were frequent while significant TP53 and KIT variants were not detected (p = 0.0003).
WT1 has been identified as a novel factor involved in TGCT pathogenesis, with a potential prognostic impact. Distinct biologic nature of the two types of relapses occurring in TGCT has been demonstrated. Differential mutation rate of the key TGCT-related genes has been documented.
威尔姆斯瘤基因1（WT1）是一种对睾丸发育和功能至关重要的锌指转录因子，本研究联合其他基因探讨它们在睾丸生殖细胞肿瘤（TGCT）发病机制中的作用。
共研究了284例TGCT样本和100例对照样本，包括对WT1表达和BRAF突变进行定量聚合酶链反应（qPCR）、p53免疫组织化学检测以及大规模平行扩增子测序。
WT1在TGCT中显著低表达（p < 0.0001），缺乏外显子5的异构体比例增加，在初治复发的TGCT患者中水平较低，而在化疗预处理复发的患者中水平较高。仅在1%的患者中检测到BRAF V600E突变。与匹配的原发性肿瘤相比，p53蛋白在TGCT转移灶中低表达。在9个选定的与TGCT相关的基因中，RAS/BRAF和WT1突变较为常见，而未检测到显著的TP53和KIT变异（p = 0.0003）。
WT1已被确定为参与TGCT发病机制的新因素，具有潜在的预后影响。已证实TGCT中发生的两种复发具有不同的生物学特性。记录了关键TGCT相关基因的差异突变率。
