Guidelines for the Li–Fraumeni and heritable TP53-related cancer syndromes

[en] Fifty years after the recognition of the Li–Fraumeni syndrome (LFS), our perception of cancers related to germline alterations of TP53 has drastically changed: (i) germline TP53 alterations are often identified among children with cancers, in particular soft-tissue sarcomas, adrenocortical carcinomas, central nervous system tumours, or among adult females with early breast cancers, without familial history. This justifies the expansion of the LFS concept to a wider cancer predisposition syndrome designated heritable TP53-related cancer (hTP53rc) syndrome; (ii) the interpretation of germline TP53 variants remains challenging and should integrate epidemiological, phenotypical, bioinformatics prediction, and functional data; (iii) the penetrance of germline disease-causing TP53 variants is variable, depending both on the type of variant (dominant-negative variants being associated with a higher cancer risk) and on modifying factors; (iv) whole-body MRI (WBMRI) allows early detection of tumours in variant carriers and (v) in cancer patients with germline disease-causing TP53 variants, radiotherapy, and conventional genotoxic chemotherapy contribute to the development of subsequent primary tumours. It is critical to perform TP53 testing before the initiation of treatment in order to avoid in carriers, if possible, radiotherapy and genotoxic chemotherapies. In children, the recommendations are to perform clinical examination and abdominal ultrasound every 6 months, annual WBMRI and brain MRI from the first year of life, if the TP53 variant is known to be associated with childhood cancers. In adults, the surveillance should include every year clinical examination, WBMRI, breast MRI in females from 20 until 65 years and brain MRI until 50 years. © 2020, The Author(s).

Disciplines :

Genetics & genetic processes

Author, co-author :

Frebourg, T.; Department of Genetics, Rouen University Hospital and Inserm U1245, Normandie University, UNIROUEN, Normandy Centre for Genomic and Personalized Medicine, Rouen, France

Bajalica Lagercrantz, S.; Hereditary Cancer Unit, Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden, Karolinska University Hospital, Stockholm, Sweden

Oliveira, C.; i3S—Instituto de Investigação e Inovação em Saúde & Institute of Molecular Pathology and Immunology of the University of Porto, and Porto Comprehensive Cancer Center, Porto, Portugal

Magenheim, R.; Community Representative, Berlin, Germany

Evans, D. G.; Manchester Centre for Genomic Medicine, Division of Evolution and Genomic Sciences, University of Manchester, MAHSC, St Mary’s Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom

Hoogerbrugge, N.; Radboud University Medical Center, Nijmegen, Netherlands

Ligtenberg, M.; Radboud University Medical Center, Nijmegen, Netherlands

Kets, M.; Radboud University Medical Center, Nijmegen, Netherlands, NKI Antoni van Leeuwenhoek hospital, Amsterdam, Netherlands

Oostenbrink, R.; Erasmus Medical Center, Rotterdam, Netherlands

Sijmons, R.; University Medical Center, Groningen, Netherlands

More authors (37 more)

Language :

English

Title :

Guidelines for the Li–Fraumeni and heritable TP53-related cancer syndromes

Publication date :

2020

Journal title :

European Journal of Human Genetics

ISSN :

1018-4813

eISSN :

1476-5438

Publisher :

Springer Nature

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

CE - Commission Européenne [BE]

Available on ORBi :

since 04 September 2020

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