Study from the German Cancer Predisposition Registry: The type of TP53 variant matters
Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome that is caused by pathogenic TP53 variants and is associated with a massively increased cancer risk. It represents one of the most important genetic causes of cancer in children and adults. Modern DNA sequencing methods are repeatedly uncovering pathogenic TP53 germline variants in individuals who do not meet previously established clinical LFS testing criteria. This has led to a "Li-Fraumeni Spectrum" classification that reflects the disease spectrum and takes into account atypical and attenuated LFS courses.
The new classification has now been applied for the first time using data from the German Cancer Predisposition Registry. In the study led by Professor Dr. Christian Kratz, Director of the Department of Paediatric Haematology and Oncology at Hannover Medical School (MHH), the research team analysed factors that influence the cancer risk within the Li-Fraumeni spectrum. In the process, the researchers were able to demonstrate significant differences in the TP53 variant spectrum in patients with severe compared to patients with less severe disease courses.
The type of TP53 variant is decisive
"Differences in the severity of the disease courses correlate with the underlying TP53 variant type," explains Dr. Judith Penkert, first author of the study, which was published in the renowned journal Journal of Hematology & Oncology. "Our data suggest that in the future, more comprehensive genotype-phenotype correlations in large, international cohorts could enable more accurate cancer risk prediction," says Penkert from the Institute of Human Genetics, who is currently conducting research in Professor Kratz's team.
A total of 141 people from 94 families with disease-causing TP53 variants were analysed. "73 families fulfilled the criteria for an LFS. In 21 families we were able to diagnose an attenuated LFS. According to previously used LFS test criteria, the diagnosis would not have been missed in these individuals," says Penkert.
LFS test criteria should be adapted
"Our results help to better predict the cancer risk associated with specific TP53 variants in the future, so that cancer surveillance can be adapted to the individual risk," says Kratz. "The finding that a substantial proportion of patients are missed when using the previously established LFS test criteria suggests that the criteria need to be revised," emphasises Professor Kratz, who, besides others, was in involved in the development of the Li-Fraumeni spectrum classification.
For further information, please contact Professor Dr. Christian Kratz, telephone (0511) 532-6712, email@example.com.
The original paper can be found here.
The original paper on the Li-Fraumeni spectrum can be found here.