Role of the ATM gene in radiation sensitivity, relevance to breast cancer treatment
© Current Science Ltd 2000
Published: 12 March 2000
Clinical observations of normal tissue damage are observed in a subset of patients following radiotherapy, with several studies reporting that up to 10% of breast cancer patients show early or late tissue reactions. Mutations in the Ataxia telangiectasia gene (ATM) result in extreme radiation sensitivity: homozygotes are predisposed to developing cancers at a young age and show an acute radiation reaction when treated with conventional radiotherapeutic doses for cancer. Heterozygotes have an increased cancer risk, in particular breast cancer, and some degree of sensitivity to ionising radiation (IR) has been reported in in vitro studies. To evaluate the potential role of the ATM gene in breast cancer development and the radiosensitivity seen in certain breast cancer cases, we have established lymphoblastoid cell lines (LCL) from radiosensitive (EORTC >3) and non-radiosensitive breast cancer patients. In some of the LCLs established from radiation sensitive breast cancer patients, the level of cell survival and the p53 induction after IR exposure are lower than those observed in control cell lines, indicative of an alteration in the ATM signalling pathway. No ATM mutations were detected in the LCLs from the 10 non-radiosensitive breast cancer patients, whereas one truncating mutation and 3 nucleotide changes were found in 4 out of 27 LCLs from the radiosensitive patients. The frequency of these nucleotide alterations in the general population is being established, in order to determine whether they represent cancer and/or radiation sensitivity predisposing mutations.
Financial support to JH from the Association pour la Recherche sur le Cancer and La Ligue Nationale Contre le Cancer, Comité Départemental du Rhône is gratefully acknowledged.