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A new type of cluster analysis makes customised cancer screening tests possible.
People with the rare Li-Fraumeni syndrome (LFS) have a high risk of developing cancer. Almost all those affected will develop cancer once, and in many cases several times, during their lifetime. LFS is a hereditary disease caused by disease-relevant variants in the TP53 gene. Researchers at Hannover Medical School (MHH) have now analysed the disease severity triggered by these TP53 gene variants in a large study involving 304 affected individuals. ‘Our results will probably have a direct impact on clinical care. We can now better assess the risk of cancer and plan to adapt early detection examinations to the individual risk,’ explains Prof. Dr Christian Kratz, Director of the Department of Paediatric Haematology and Oncology at the MHH and initiator of the study. He is receiving support for his research from the Federal Ministry of Education and Research and the German Paediatric Cancer Foundation.
Different degrees of loss of function in the gene variants
The individual gene variants were divided into different clusters. The method used was recently described in detail in a study (https://www.sciencedirect.com/science/article/pii/S2589004224025215?via%3Dihub) by French co-operation partners of the MHH. This analysis divides TP53 variants into different groups with varying degrees of loss of function of the altered protein. Among other things, it became clear that carriers of cluster C variants developed cancer significantly later than carriers of variants from other groups (see yellow line in the figure).
Customise cancer prevention and monitoring
People with LFS typically develop brain tumours, adrenocortical carcinoma, soft tissue sarcoma, osteosarcoma and breast cancer. Those affected also have an increased risk of haematological, gastrointestinal, skin, lung, prostate, pancreatic and other cancers. In LFS, cancer often occurs in childhood or adolescence. Comprehensive early cancer detection measures are recommended for those affected.
The biologically plausible results of this study can serve as a basis for future recommendations on cancer prevention and monitoring. ‘For example, whole-body magnetic resonance imaging may not be necessary for carriers of disease-relevant group C variants until the age of 18. It may be sufficient to screen affected children with these specific variants for adrenocortical carcinoma. Later in life, however, a full surveillance programme is required,’ explains Lucas John Müntnich, assistant physician at the Department of Paediatric Haematology and Oncology and first author of the study.
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You can findthe original publication here: https://academic.oup.com/jncics/article/9/1/pkaf008/7985583?utm_source=etoc&...
For further information, please contact Prof Dr Christian Kratz, Kratz.Christian@mh-hannover.de.
The two MHH researchers Lucas John Müntnich and Professor Christian Kratz refer to the cluster analy ...
Copyright: Karin Kaiser/MHH
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The two MHH researchers Lucas John Müntnich and Professor Christian Kratz refer to the cluster analy ...
Copyright: Karin Kaiser/MHH
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