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  • Title: Wilms tumor gene 1 (WT1), TP53, RAS/BRAF and KIT aberrations in testicular germ cell tumors.
    Author: 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.
    Journal: Cancer Lett; 2016 Jul 01; 376(2):367-76. PubMed ID: 27085458.
    Abstract:
    PURPOSE: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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