title: ID3 contributes to cerebrospinal fluid seeding and poor prognosis in medulloblastoma.
abstract: BACKGROUND
  The inhibitor of differentiation (ID) genes have been implicated as promoters of tumor progression and metastasis in many human cancers. The current study investigated the expression and functional roles of ID genes in seeding and prognosis of medulloblastoma.
  
  
  METHODS
  ID gene expression was screened in human medulloblastoma tissues. Knockdown of ID3 gene was performed in medulloblastoma cells in vitro. The expression of metastasis-related genes after ID3 knockdown was assessed. The effect of ID3 knockdown on tumor seeding was observed in an animal model in vivo. The survival of medulloblastoma patients was plotted according to the ID3 expression levels.
  
  
  RESULTS
  Significantly higher ID3 expression was observed in medulloblastoma with cerebrospinal fluid seeding than tumors without seeding. Knockdown of ID3 decreased proliferation, increased apoptosis, and suppressed the migration of D283 medulloblastoma cells in vitro. In a seeding model of medulloblastoma, ID3 knockdown in vivo with shRNA inhibited the growth of primary tumors, prevented the development of leptomeningeal seeding, and prolonged animal survival. High ID3 expression was associated with shorter survival of medulloblastoma patients, especially in Group 4 medulloblastomas.
  
  
  CONCLUSIONS
  High ID3 expression is associated with medulloblastoma seeding and is a poor prognostic factor, especially in patients with Group 4 tumors. ID3 may represent the metastatic/ aggressive phenotype of a subgroup of medulloblastoma.
authors.affiliation: Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul, Republic of Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Phi
authors.forename: Seung Ah
authors.initials: SA
authors.lastname: Choi
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Lim
authors.forename: Joongyub
authors.initials: J
authors.lastname: Lee
authors.forename: Kyu-Chang
authors.initials: KC
authors.lastname: Wang
authors.forename: Sung-Hye
authors.initials: SH
authors.lastname: Park
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002528:Cerebellar Neoplasms / Q000134:cerebrospinal fluid / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051796:Inhibitor of Differentiation Proteins / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008527:Medulloblastoma / Q000134:cerebrospinal fluid / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D014183:Transplantation, Heterologous
chemical_list: D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C075640:ID3 protein, human