RASSF1A methylation indicates a poor prognosis in hepatoblastoma patients
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The RAS association domain family protein 1 (RASSF1A) is known to be frequently inactivated by promoter hypermethylation in cancers. This study investigated the association of RASSF1A methylation with clinical outcomes in hepatoblastoma patients and whether it is correlated with the histological phenotype of hepatoblastoma tumors.
Seventy-four hepatoblastoma tumors were obtained from patients enrolled in the Japanese study group for pediatric liver tumor protocol-2. From nine formalin-fixed, paraffin-embedded specimens, we extracted DNA by dissection under a light microscope. We examined the methylation status of the RASSF1A promoter region by bisulfite pyrosequencing.
Twenty-five (33.8 %) hepatoblastoma tumors were classified as having methylated RASSF1A. The RASSF1A methylation was significantly associated with metastatic tumors and a poor prognosis. Despite the complete resection, five pretreatment extent of disease II tumors showed recurrence or distant metastasis postoperatively. Among these cases, four tumors were found to show RASSF1A methylation. When compared to histologically different types of cell, RASSF1A methylation values in samples of the normal liver, fetal type, and embryonal type, were significantly elevated in ascending order.
We confirmed that RASSF1A methylation is a significant prognostic indicator in hepatoblastomas, and it may become a promising molecular marker to stratify patients into appropriate risk groups.
KeywordsHepatoblastoma RASSF1A methylation Prognostic marker
We would like to thank all the staff at institutes that participated in JPLT for enrolling their patients in the study. We are also grateful to JPLT steering committee members (Drs. T. Hishiki, K. Ida, K. Watanabe, S. Kondo, T. Oue, M. Yano, and T. Tajiri), JPLT pathological committee members (Drs. H. Horie, Y. Tanaka, and K. Inoue) and a data administrator for JPLT (Dr. K. Hiyama, Hiroshima University), for data managements and clinic-pathological review of these patients.
Conflict of interest
The authors who have taken part in this study declare that they do not have anything to disclose regarding funding or any conflict of interest with respect to this manuscript. The first and the corresponding authors are JSPS members, and this abstract was selected for presentation at the 50th Annual Meeting of the Japanese Society of Pediatric Surgeons.
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