Jan Gödeke1, Elke Luxenburger1, Franziska Trippel1, Kristina Becker1, Beate Häberle1, Josef Müller-Höcker2, Dietrich von Schweinitz1, Roland Kappler3. 1. Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Lindwurmstr. 2a, 80337, Munich, Germany. 2. Institute of Pathology, Ludwig-Maximilians-University Munich, Thalkirchner Str. 36, 80337, Munich, Germany. 3. Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Lindwurmstr. 2a, 80337, Munich, Germany. roland.kappler@med.uni-muenchen.de.
Abstract
BACKGROUND/PURPOSE OF THE STUDY: Despite tremendous progress in therapy, about 30% of patients with hepatoblastoma still succumb to the disease. Thus, the development of improved therapies as well as the identification of prognostic factors are urgently needed. METHODS: In the present study, expression and promoter methylation of the N-myc downstream-regulated gene (NDRG2), a tumor suppressor gene contributing to the regulation of the Wnt signalling pathway, was analysed in 38 hepatoblastoma samples by real-time reverse transcription-PCR and pyrosequencing, respectively. RESULTS: The NDRG2 gene was highly expressed in normal pediatric liver tissue, but was significantly downregulated in heptoblastoma primary tumors. Detailed methylation analysis of CpG sites in the NDRG2 promoter region revealed a general high degree of DNA methylation in hepatoblastoma, which correlated with the suppression of NDRG2. By analyzing clinicopathological features we could demonstrate a strong association between low NDRG2 expression and tumor metastasis. Importantly, the overall survival analysis by Kaplan-Meier revealed that high NDRG2 expression was correlated with a higher survival rate in hepatoblastoma patients. CONCLUSION: Our data show that downregulation of NDRG2 may play an important role in advanced hepatoblastomas.
BACKGROUND/PURPOSE OF THE STUDY: Despite tremendous progress in therapy, about 30% of patients with hepatoblastoma still succumb to the disease. Thus, the development of improved therapies as well as the identification of prognostic factors are urgently needed. METHODS: In the present study, expression and promoter methylation of the N-myc downstream-regulated gene (NDRG2), a tumor suppressor gene contributing to the regulation of the Wnt signalling pathway, was analysed in 38 hepatoblastoma samples by real-time reverse transcription-PCR and pyrosequencing, respectively. RESULTS: The NDRG2 gene was highly expressed in normal pediatric liver tissue, but was significantly downregulated in heptoblastoma primary tumors. Detailed methylation analysis of CpG sites in the NDRG2 promoter region revealed a general high degree of DNA methylation in hepatoblastoma, which correlated with the suppression of NDRG2. By analyzing clinicopathological features we could demonstrate a strong association between low NDRG2 expression and tumor metastasis. Importantly, the overall survival analysis by Kaplan-Meier revealed that high NDRG2 expression was correlated with a higher survival rate in hepatoblastoma patients. CONCLUSION: Our data show that downregulation of NDRG2 may play an important role in advanced hepatoblastomas.
Authors: Melanie Eichenmüller; Franziska Trippel; Michaela Kreuder; Alexander Beck; Thomas Schwarzmayr; Beate Häberle; Stefano Cairo; Ivo Leuschner; Dietrich von Schweinitz; Tim M Strom; Roland Kappler Journal: J Hepatol Date: 2014-08-15 Impact factor: 25.083
Authors: Soo-Kyung Shon; Aeyung Kim; Ji Young Kim; Keun Il Kim; Young Yang; Jong-Seok Lim Journal: Biochem Biophys Res Commun Date: 2009-05-19 Impact factor: 3.575