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

Abstract

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.

Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes

“…In patients harbouring germline TP53 mutations, several studies have highlighted the risk of secondary tumours in the field of radiotherapy suggesting that, in a breast patient with germline TP53 mutation, radiotherapy should be avoided. [35][36][37] This is a strong additional argument justifying the inclusion of TP53 in a diagnostic NGS panel for breast cancer. Nevertheless, considering the wide LFS tumour spectrum and tumour risk in children, TP53 testing should be carefully considered and the medical implications of a positive test should be clearly explained to the patient before the test.…”

p53 and disease: when the guardian angel fails

“…This increased susceptibility to IR also needs to be borne in mind when treating tumors from young LFS patients, as these individuals are at high risk of second malignancies. 23 Prenatal or pre-implantation genetic testing can be offered to fertile couples affected by LFS. Moreover, as mentioned above, determining the exact nature of the TP53 mutation may be of prognostic significance and therefore important for the clinical management of these patients.…”

Identification and characterization of a novel germline p53 mutation in a patient with glioblastoma and colon cancer

“…1 Germline mutations in the p53 tumor suppressor gene have been identified in patients with LFS and patients with Li-Fraumeni-like syndrome (LFL). [2][3][4][5] However, to date, germline p53 mutations in patients not fulfilling the criteria of LFS or LFL have been reported only very rarely. 6 In the present study, we identified a novel germline p53 mutation in a patient with a glioblastoma and colon cancer, whose family history was not consistent with either LFS or LFL, examined p53 allelic status and p53 protein expression in the tumors and evaluated the functional activities of the novel mutant p53.…”