Three-hit hypothesis in astrocytoma: tracing the polymorphism D1853N in ATM gene through a pedigree of the proband affected with primary brain tumor

J Cancer Res Clin Oncol. 2008 Nov;134(11):1173-80. doi: 10.1007/s00432-008-0404-4. Epub 2008 May 9.

Abstract

Ataxia telangictasia mutated (ATM) is involved in DNA repair pathway and cell-cycle checkpoints. ATM alterations were found in medulloblastomas, gliomas, but not in astrocytoma. The polymorphism D1853N was reported in healthy individuals and medulloblastomas. We could observe this polymorphism, heterozygously, in a proband affected with astrocytoma and traced it through her pedigree. We propose the three-hit hypothesis as a triangle initiators includes D1853N as a first predisposing hit, IVS 38- 63T --> A as a second hit deriving from the first somatic evolution before differentiation and IVS 38- 30 A --> G as a third hit through the development of an astrocytoma. In addition, the D1853N polymorphism was occurred in different allele from IVS 38- 63T --> A and IVS 38- 30 A --> G.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Astrocytoma / blood
  • Astrocytoma / genetics*
  • Astrocytoma / pathology
  • Ataxia Telangiectasia Mutated Proteins
  • Brain Neoplasms / blood
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Cell Cycle / genetics
  • Cell Cycle Proteins / genetics*
  • Cloning, Molecular
  • DNA Repair
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / isolation & purification
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Amplification
  • Humans
  • Immunohistochemistry
  • Male
  • Pedigree
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Protein Serine-Threonine Kinases / genetics*
  • Tumor Suppressor Proteins / genetics*

Substances

  • Cell Cycle Proteins
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases