Hungarian Scientific Research Grant(NRDI FK135065)
New National Excellence Program of the Ministry of Human Capacities(UNKP-22-5-SE-1)
(National Tumor Biology Laboratory, NLP-17) Támogató: The Hungarian National Laboratories
Excellence program
(2020-1.1.6-JÖVŐ-2021-00003) Támogató: NKFIH
Szakterületek:
Onkológia
TP53 variant interpretation is still challenging, especially in patients with attenuated
Li-Fraumeni syndrome (LFS). We investigated the prevalence of pathogenic/likely pathogenic
(P/LP) variants and LFS disease in the Hungarian population of cancer patients. By
testing 893 patients with multiplex or familial cancer, we identified and functionally
characterized novel splice variants of TP53 helping accurate variant classification.
The differences among various semi-automated interpretation platforms without manual
curation highlight the importance of focused interpretation as the automatic classification
systems do not apply the TP53-specific criteria. The predicted frequency of the TP53
P/LP variants in Hungary is 0.3 per million which most likely underestimates the real
prevalence. The higher detection rate of disease-causing variants in patients with
attenuated LFS phenotype compared to the control population (OR 12.5; p < 0.0001)
may raise the potential benefit of the TP53 genetic testing as part of the hereditary
cancer panels of patients with multiple or familial cancer even when they do not meet
Chompret criteria. Tumours developed at an earlier age in phenotypic LFS patients
compared to the attenuated LFS patients which complicates genetic counselling as currently
there are no different recommendations in surveillance protocols for LFS, phenotypic
LFS, and attenuated LFS patients.
