Two metachronous tumors in the radiotherapy fields of a patient with Li-Fraumeni syndrome

Int J Cancer. 2001 Aug 20;96(4):238-42. doi: 10.1002/ijc.1021.


A woman with a family history of brain tumors in her daughter and sister presented with a breast cancer. She subsequently developed two metachronous primary tumors: a small-cell lung cancer and a colon carcinoma. These tumors arose within the internal mammary radiotherapy field and within the field irradiated for ovariolysis. The p53 gene was analyzed in whole blood lymphocytes using a functional assay developed in yeast Saccharomyces cerevisiae, which tests the transcriptional competence of p53. DNA from the colon cancer cells was analyzed by polymerase chain reaction and sequencing. The patient had a germline-inactivating p53 mutation, confirming the diagnosis of Li-Fraumeni syndrome (LFS). The colon tumor and the lung tumor both conserved the mutant p53 allele but had lost the wild-type allele. This observation and the experimental data suggest an abnormal sensitivity of LFS patients to radiogenic carcinogenesis. The indications and extent of radiotherapy in patients with a clinical or molecular diagnosis of LFS should be discussed individually and should take into account the risk of secondary neoplasms arising in the radiation fields.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Alleles
  • Amino Acid Sequence
  • Base Sequence
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / radiotherapy*
  • Carcinoma, Small Cell / etiology*
  • Carcinoma, Small Cell / secondary*
  • Colonic Neoplasms / etiology*
  • Colonic Neoplasms / secondary*
  • DNA Mutational Analysis
  • Exons
  • Family Health
  • Female
  • Genes, p53 / genetics
  • Germ-Line Mutation
  • Humans
  • Li-Fraumeni Syndrome / complications*
  • Li-Fraumeni Syndrome / genetics*
  • Lung Neoplasms / etiology*
  • Lung Neoplasms / secondary*
  • Molecular Sequence Data
  • Mutation
  • Neoplasms, Radiation-Induced*
  • Radiotherapy / adverse effects
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid