p53 Tetramerization domain mutations: germline R342X and R342P, and somatic R337G identified in pediatric patients with Li-Fraumeni syndrome and a child with adrenocortical carcinoma

Fam Cancer. 2009;8(4):541-6. doi: 10.1007/s10689-009-9284-2.


Germline p53 mutations are associated with Li-Fraumeni syndrome (LFS) and other familial cancer phenotypes not fulfilling the definition for LFS. The majority of germline p53 mutations cluster in exons 5-8, corresponding to a DNA binding domain. We report the identification of two germline mutations and a somatic mutation in a tetramerization domain (TD), a rare site for mutations. The germline mutation, R342X (16915C>T), and the novel mutation, R342P (16916G>C), were found in a child with adrenocortical carcinoma and in a LFS pediatric patient with multiple primaries. The novel somatic mutation, R337G (16900C>G), was discovered in myelodysplastic syndrome with transformation to acute myeloblastic leukemia, developing as the third primary in the LFS child. These findings add further information on p53 TD mutations and TD contribution to tumorigenesis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Cortex Neoplasms / genetics*
  • Adrenocortical Carcinoma / genetics*
  • Base Sequence
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Humans
  • Li-Fraumeni Syndrome / genetics*
  • Male
  • Mutation
  • Pedigree
  • Protein Structure, Tertiary / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Protein p53 / genetics*


  • Tumor Suppressor Protein p53