The TP53-ARF Tumor Suppressor Pathway Is Frequently Disrupted in large/cell Anaplastic Medulloblastoma

Brain Res Mol Brain Res. 2004 Feb 5;121(1-2):137-40. doi: 10.1016/j.molbrainres.2003.11.016.

Abstract

We analyzed the TP53 and INK4A/ARF loci in 29 pediatric medulloblastomas. Mutually exclusive mutation in TP53, methylation of P14(ARF) or deletion of INK4A/ARF were identified in 21% (6/29) of tumors. Five of these alterations were detected in large cell/anaplastic medulloblastomas or tumors with significant anaplasia. Our data provide the first evidence that alterations within the TP53-ARF tumor suppressor pathway contribute to development of aggressive forms of medulloblastoma.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anaplasia
  • Carcinoma, Large Cell / metabolism*
  • Cerebellar Neoplasms / metabolism*
  • Child
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • DNA, Neoplasm / analysis
  • Exons
  • Gene Deletion
  • Humans
  • Medulloblastoma / metabolism*
  • Methylation
  • Mutation
  • Polymerase Chain Reaction / methods
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Sequence Analysis / methods
  • Signal Transduction
  • Tumor Suppressor Protein p14ARF
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Proteins

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Neoplasm
  • RNA, Messenger
  • Tumor Suppressor Protein p14ARF
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins