p53 mosaicism with an exon 8 germline mutation in the founder of a cancer-prone pedigree

Oncogene. 1992 Nov;7(11):2169-73.


Changes in the tumor-suppressor gene p53 are frequently acquired during the course of malignant development of human tumors. Recently, constitutional heterozygous mutations in p53 exon 7 have been identified as the primary cause of cancer predisposition in cases of the familial Li-Fraumeni cancer syndrome. These findings underline the need for extensive mutation screening in families with high cancer incidence. This report describes the detection and follow-up by two-dimensional single-strand conformation polymorphism analysis (2DSSCP) of a new germline mutation of p53 exon 8 in a case of suspected Li-Fraumeni syndrome. Although a high cancer incidence had been reported in the family history of the father of siblings suffering from brain tumor and rhabdomyosarcoma, a constitutional heterozygous p53 mutation was identified only in the affected children. Retrospective analysis of archival tissue of a half-sister who died several years ago from a tumor of previously uncertain diagnosis revealed the same mutation. The mutation had therefore occurred in the germ cells of the mother, who thus appears to be a mosaic. The cancer predisposition of the paternal ancestors must have been due to other factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Base Sequence
  • Exons*
  • Female
  • Genes, p53*
  • Humans
  • Li-Fraumeni Syndrome / genetics*
  • Male
  • Molecular Sequence Data
  • Mosaicism*
  • Mutation*
  • Polymorphism, Restriction Fragment Length