Hereditary diseases/congenital diseases/mutations
tp53 - Li Fraumeni Syndrome
The presence of somatic mutations of the TP53 gene (tp53, also p53) in malignant tumors is common.In addition to somatic mutations, there are also germline mutations of the TP53 gene, which underlie Li-Fraumeni syndrome.TP53 Mutations in Human Cancers: Origins, Consequences, and Clinical Use The TP53 gene codes for the p53 protein, which is one of the most important tumor suppressors.If a mutation of the gene underlying the p53 protein causes a loss of function of the protein, apoptosis induction, DNA repair and cell cycle control are impaired.TP53 is mutated in around 50% of all human malignant tumors. p53, guardian of the genome In Li Fraumeni syndrome, a heterozygous germline mutation (autosomal dominant) of p53 is present.There are 250 different known mutations in the p53 gene with different types, but the mutations that lead to a reading frame error are the most common.The result is a very high risk of developing tumors, with 50% of women affected by the age of 31 and men by the age of 46.
![[Translate to English:] Li Fraumeni Syndrom](https://www.strahlenklinik.uk-erlangen.de/fileadmin/_processed_/7/6/csm_Li_Fraumeni_98bcc4a5a8.png)
Own studies on radiation sensitivity:
On average, patients with Li Fraumeni syndrome have significantly increased radiation sensitivity. Only three out of 11 patients have average radiation sensitivity, seven patients have increased radiation sensitivity and one patient has extremely increased radiation sensitivity.
Literature on radiosensitivity measurements:
- Radiation sensitivity of breast carcinomas during adjuvant radiotherapy
- The loss of function of the protein tp53 leads to increased resistance to ionizing radiation in the mouse model. Other studies suggesting that a functioning tp53 is important for the therapeutic success of ionizing radiation or other DNA-damaging substances confirm these observations. Breast Cancer Adjuvant Radiotherapy in BRCA1/2, TP53, ATM Genes Mutations: Are There Solved Issues?
- A tp53 mutation in tumor cells of breast carcinomas is associated with a poorer prognosis, lower overall survival, higher recurrence rates and poorer local control by radiotherapy. High radiation doses and multiple radiation therapies should be avoided in tp53 patients. Breast Cancer Adjuvant Radiotherapy in BRCA1/2, TP53, ATM Genes Mutations: Are There Solved Issues?
Literature on clinical case reports/consequences of radiation:
- Radiation sensitivity of breast carcinomas during adjuvant radiotherapy
- Although there are few data on adjuvant radiotherapy of breast cancer patients with a tp53 mutation, there are indications from in-vitro studies of an increased risk of acute radiotoxicities. There is an altered apoptosis due to ionizing radiation. Breast Cancer Adjuvant Radiotherapy in BRCA1/2, TP53, ATM Genes Mutations: Are There Solved Issues?
- Depending on the type of mutation, there is an altered risk of toxicities. Breast Cancer Adjuvant Radiotherapy in BRCA1/2, TP53, ATM Genes Mutations: Are There Solved Issues
Conclusion regarding testing for radiation sensitivity:
Li Fraumeni patients are on average more sensitive to radiation, but only to a limited extent. Extremely increased radiation sensitivities are possible, where the dose should definitely be adjusted. In addition, Li Fraumeni syndrome patients have a very high risk of developing tumors and secondary tumors after treatment. It is stated that 30% of patients develop a secondary carcinoma within a mean time of 10.7 years. It is therefore generally recommended that radiotherapy should be avoided if possible.
To learn more about radiation sensitivity in Li Fraumeni, we are very interested in testing patients with Li Fraumeni. We are also happy to test people who do not have a tumor. Please get in touch with us.