title: RASSF1A methylation indicates a poor prognosis in hepatoblastoma patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Kita-ku, Kita 15, Nishi 7, Sapporo, 060-8638, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Honda
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Miyagi
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Masashi
authors.initials: M
authors.lastname: Minato
authors.forename: Masayuki
authors.initials: M
authors.lastname: Haruta
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Kanako C
authors.initials: KC
authors.lastname: Hatanaka
authors.forename: Eiso
authors.initials: E
authors.lastname: Hiyama
authors.forename: Takehiko
authors.initials: T
authors.lastname: Kamijo
authors.forename: Tadao
authors.initials: T
authors.lastname: Okada
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D018197:Hepatoblastoma / Q000235:genetics*; D006801:Humans; D007223:Infant; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins