De novo germline TP53 mutation presenting with synchronous malignancies of the central nervous system

Pediatr Blood Cancer. 2009 Dec 15;53(7):1352-4. doi: 10.1002/pbc.22214.

Abstract

We present a case of a 14-year-old male with a germline TP53 mutation who presented with synchronous primitive neuroectodermal tumor and choroid plexus carcinoma. Identification of synchronous brain tumors prompted genetic testing for predisposition to malignancy. Within 5 months of presentation, the child developed widely metastatic alveolar rhabdomyosarcoma. Patient DNA sequencing showed a TP53 allele with a premature stop codon in the oligomerization/nuclear export signal (NES) domain (R342ter). The child's parents, younger brother, paternal grandparents, and maternal grandmother, are without history of malignancy. The patient's brother tested negative for TP53 mutations. This case identifies a rare, de novo, germline TP53 mutation presenting with synchronous CNS malignancies and exhibiting a more fulminant course than typical cases of Li-Fraumeni syndrome.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / radiotherapy
  • Brain Neoplasms / surgery
  • Carcinoma / drug therapy
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Carcinoma / radiotherapy
  • Choroid Plexus Neoplasms / drug therapy
  • Choroid Plexus Neoplasms / genetics*
  • Choroid Plexus Neoplasms / pathology
  • Choroid Plexus Neoplasms / radiotherapy
  • Cisplatin / administration & dosage
  • Codon, Nonsense*
  • Combined Modality Therapy
  • Cranial Irradiation
  • Fatal Outcome
  • Frontal Lobe / pathology
  • Frontal Lobe / surgery
  • Genes, p53*
  • Germ-Line Mutation*
  • Humans
  • Lomustine / administration & dosage
  • Male
  • Neoplasms, Multiple Primary / genetics*
  • Neoplasms, Multiple Primary / pathology
  • Neoplasms, Multiple Primary / therapy
  • Neoplasms, Unknown Primary / genetics
  • Neuroectodermal Tumors, Primitive / genetics*
  • Neuroectodermal Tumors, Primitive / pathology
  • Neuroectodermal Tumors, Primitive / surgery
  • Radiotherapy, Adjuvant
  • Rhabdomyosarcoma, Alveolar / genetics*
  • Rhabdomyosarcoma, Alveolar / secondary*
  • Spinal Neoplasms / drug therapy
  • Spinal Neoplasms / radiotherapy
  • Spinal Neoplasms / secondary
  • Vincristine / administration & dosage

Substances

  • Codon, Nonsense
  • Vincristine
  • Lomustine
  • Cisplatin