L Boublikova1, V Bakardjieva-Mihaylova2, K Skvarova Kramarzova2, D Kuzilkova2, A Dobiasova2, K Fiser2, J Stuchly2, M Kotrova2, T Buchler3, P Dusek4, M Grega5, B Rosova6, Z Vernerova7, P Klezl8, M Pesl9, R Zachoval10, M Krolupper11, M Kubecova12, V Stahalova13, J Abrahamova3, M Babjuk4, R Kodet5, J Trka2. 1. Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic. Electronic address: ludmila.boublikova@lfmotol.cuni.cz. 2. Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic. 3. Department of Oncology, 1st Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic. 4. Department of Urology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic. 5. Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic. 6. Department of Pathology and Molecular Medicine, Thomayer Hospital, Prague, Czech Republic. 7. Department of Pathology, 3rd Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady, Prague, Czech Republic. 8. Department of Urology, 3rd Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady, Prague, Czech Republic. 9. Department of Urology, 1st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. 10. Department of Urology, Thomayer Hospital, Prague, Czech Republic. 11. Department of Urology, Na Bulovce Hospital, Prague, Czech Republic. 12. Department of Oncology and Radiotherapy, 3rd Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady, Prague, Czech Republic. 13. Institute of Radiotherapy and Oncology, 1st Faculty of Medicine, Charles University and Na Bulovce Hospital, Prague, Czech Republic.
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.
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. BRAFV600E 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.
Authors: Todd L Edwards; Ayush Giri; Jacklyn N Hellwege; Katherine E Hartmann; Elizabeth A Stewart; Janina M Jeff; Michael J Bray; Sarah A Pendergrass; Eric S Torstenson; Jacob M Keaton; Sarah H Jones; Radhika P Gogoi; Helena Kuivaniemi; Kathryn L Jackson; Abel N Kho; Iftikhar J Kullo; Catherine A McCarty; Hae Kyung Im; Jennifer A Pacheco; Jyotishman Pathak; Marc S Williams; Gerard Tromp; Eimear E Kenny; Peggy L Peissig; Joshua C Denny; Dan M Roden; Digna R Velez Edwards Journal: Front Genet Date: 2019-06-12 Impact factor: 4.599
Authors: Violeta Bakardjieva-Mihaylova; Karolina Skvarova Kramarzova; Martina Slamova; Michael Svaton; Katerina Rejlova; Marketa Zaliova; Alena Dobiasova; Karel Fiser; Jan Stuchly; Marek Grega; Blanka Rosova; Roman Zachoval; Petr Klezl; Vaclav Eis; Eva Kindlova; Tomas Buchler; Jan Trka; Ludmila Boublikova Journal: Cancers (Basel) Date: 2019-09-06 Impact factor: 6.639