SEOM clinical guideline on heritable TP53-related cancer syndrome - 2022

Sep 24, 2026

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Li-Fraumeni syndrome is driven by heterozygous germline pathogenic variants in TP53 and confers a high lifetime risk of malignant tumors across childhood and adulthood, including premenopausal breast cancer, soft tissue sarcomas, osteosarcomas, central nervous system tumors, and adrenocortical carcinomas. Because clinical manifestations vary and do not always match classic Li-Fraumeni criteria, the syndrome concept extends to hereditable TP53-related cancer (hTP53rc). This guideline provides a basis for interpreting TP53 pathogenic variants and offers recommendations for risk-adjusted screening and prevention in carriers.

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Abstract

Introduction

TP53 gene testing

Clinical and Translational Oncology (2023) 25:2627–2633 [https://doi.org/10.1007/s12094-023-03202-9](https://doi.org/10.1007/s12094-023-03202-9) SEOM clinical guideline on heritable TP53‑related cancer syndrome (2022) Ana Beatriz Sánchez‑Heras1 · Teresa Ramon y Cajal2 · Marta Pineda3,4 · Elena Aguirre5 · Begoña Graña6 · Isabel Chirivella7 · Judit Balmaña8 · Joan Brunet3,4,9,10 on behalf of the SEOM Hereditary Cancer Working Group and AEGH Hereditary Cancer Committee Received: 11 April 2023 / Accepted: 11 April 2023 / Published online: 3 May 2023 © The Author(s) 2023 Abstract Li-Fraumeni syndrome is caused by heterozygous germline pathogenic variants in the TP53 gene. It involves a high risk of a variety of malignant tumors in childhood and adulthood, the main ones being premenopausal breast cancer, soft tissue sarcomas and osteosarcomas, central nervous system tumors, and adrenocortical carcinomas. The variability of the associated clinical manifestations, which do not always fit the classic criteria of Li-Fraumeni syndrome, has led the concept of SLF to extend to a more overarching cancer predisposition syndrome, termed hereditable TP53-related cancer syndrome (hTP53rc). However, prospective studies are needed to assess genotype–phenotype characteristics, as well as to evaluate and validate risk-adjusted recommendations. This guideline aims to establish the basis for interpreting pathogenic variants in the TP53 gene and provide recommendations for effective screening and prevention of associated cancers in carrier individuals. Keywords Li-Fraumeni syndrome · TP53 · Cancer · Pathogenic variants * Joan Brunet jbrunet@iconcologia.net Ana Beatriz Sánchez-Heras [zrtbns@gmail.com](zrtbns@gmail.com) Teresa Ramon y Cajal [tramon@santpau.cat](tramon@santpau.cat) Marta Pineda [mpineda@iconcologia.net](mpineda@iconcologia.net) Elena Aguirre [elenaaguirreortega@yahoo.es](elenaaguirreortega@yahoo.es) Begoña Graña [begona.grana.suarez@gmail.com](begona.grana.suarez@gmail.com) Isabel Chirivella [chirivella_isa@gva.es](chirivella_isa@gva.es) Judit Balmaña [jbalmana@vhio.net](jbalmana@vhio.net); [cnoguera@vhio.net](cnoguera@vhio.net) 1 Medical Oncology Department, Hospital General Universitario de Elche, Elche, Alicante, Spain 2 Medical Oncology Service, Hospital Sant Pau, Barcelona, Spain 3 Hereditary Cancer Program, Catalan Institute of Oncology, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), ONCOBELL Program, L’Hospitalet de Llobregat, Barcelona, Spain 4 Consortium for Biomedical Research in Cancer, CIBERONC, Carlos III Institute of Health, Madrid, Spain 5 Medical Oncology Department, Hospital Quironsalud, Zaragoza, Spain 6 Medical Oncology Department, University Hospital A Coruña, 15006 A Coruña, Spain 7 Medical Oncology Department, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain 8 Medical Oncology Department, Hospital Vall d’Hebron, and Hereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology, Barcelona, Spain 9 Medical Oncology Department, Catalan Institute of Oncology, University Hospital Josep Trueta, University of Girona, Girona, Spain 10 Hereditary Cancer Program, Catalan Institute of Oncology, Girona Biomedical Research Instiute (IDIBGI), Girona, Spain Introduction Li-Fraumeni syndrome (LFS) is characterized by a high risk of developing a wide variety of malignant tumors in childhood and adulthood, caused by heterozygous germline pathogenic variants in the TP53 gene. Based on penetrance data from familial presentation cases, the highest cumulative incidences in females are 56% and 15% for breast cancer (BC) and soft tissue sarcoma (STS) respectively, while in males, they said incidences are 20% both for STS and for brain cancer [1] . The predominant cancers in people with LFS are osteosarcoma and STS, premenopausal BC, brain tumors, and adrenocortical carcinoma (ACC); similarly, rare tumors, such as choroid

FAQs

What causes Li-Fraumeni syndrome in this guideline?

It is caused by heterozygous germline pathogenic variants in the TP53 gene. These variants lead to a high risk of multiple malignant tumors across childhood and adulthood.

Why does the guideline use the broader concept of hTP53rc?

Associated clinical manifestations can vary and may not always fit classic Li-Fraumeni criteria. This variability supports extending the concept to hereditable TP53-related cancer (hTP53rc).

Who should be tested for germline TP53 variants?

Patients meeting the modified Chompret Criteria should be tested. Testing is also recommended for individuals who develop a second primary tumor within a radiotherapy field, for adults via cascade testing, and for certain childhood/adolescent cancer presentations.

Sep 24, 2026

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