Bone sarcomas and cancer predisposition syndromes.

Sarah Winter, Laurence Brugières, Camille Tlemsani, Marion Gauthier-Villars, Nadège Corradini, Caroline Michot, Geneviève Baujat, Franck Bourdeaut, Thierry Leblanc, Gaëlle Bougeard, Philippe Denizeau, Brigitte Bressac, Tiphaine Adam de Beaumais, Aymeric Rouchaud, Fadila Mihoubi-Bouvier, Edwige Kasper

Journal: Bulletin du cancer 2025;112(6):664-680

PMID: 39848894

Full Text on Elsevier Science View on PubMed

Abstract

Bone sarcomas, constituting less than 1% of malignant neoplasms across all age groups, are rare tumours possibly associated with genetic susceptibility syndromes. This review aims to provide recommendations for the detection of cancer predisposition syndromes associated with bone sarcomas and managing affected patients. Recommendations were formulated by a multidisciplinary working and reviewing group from GroupOs and SFCE oncogenetic's group, including geneticists, oncologists, and radiologists. For various bone sarcomas including osteosarcomas, chondrosarcomas and Ewing sarcomas, we delineate tumour presentation, management strategies, and follow-up within the context of cancer predisposition syndromes. The inherited predisposition syndrome, associated with germline TP53 variants, known as the Li-Fraumeni syndrome, is the most frequent implicated in osteosarcoma cases. Other cancer predisposition syndromes, such as RB1, RECQ or CDKN2A disorders in osteosarcomas and Ollier and Maffucci diseases in chondrosarcomas, are also recognized. Additionally, we discuss rarer cancer predisposition syndromes associated with bone sarcomas and suggest tailored treatment approaches in some cancer predisposition syndromes to mitigate severe toxicities or secondary oncological events. Furthermore, we emphasize the role of identification somatic molecular variations in identifying constitutional germline variants and describe national and international screening programs, reference networks and molecular tumour boards available for collegial and collaborative management discussion. This comprehensive review provides insights into the intricate interplay between genetic predisposition, tumour biology, and therapeutic interventions in bone sarcoma patients with cancer predisposition syndrome.

Address: Department of Medical Oncology, Cochin Hospital, Paris Cancer Institute CARPEM, AP-HP, Université Paris Cité, Paris, France; Institut Cochin, Inserm U1016, CNRS UMR8104, CARPEM, Université Paris Cité, Paris, France.; Department of Genetics, Inserm U1245, CHU de Rouen, Normandie Université, Université Rouen Normandie, 76000 Rouen, France.; Department of Genetics, Institut Curie, PSL Research University, Paris, France.; Department of Medical Genetic, Centre Hospitalier Universitaire de Rennes, Rennes, France.; SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer) Institut Curie, PSL University, Paris, France.; Reference Center for Skeletal Dysplasia, Necker-Enfants-Malades Hospital, AP-HP, 75015 Paris, France.; Biopathology Department, Inserm U1279, Gustave-Roussy, Paris-Saclay University, 94805 Villejuif, France.; Department of Children and Adolescents Oncology, Gustave-Roussy, Villejuif, France.; Department of Radiology (IMVOC), Clinique du Val d'Ouest, Écully, France.; Department of Diagnostic and Interventional Musculoskeletal Radiology, Cochin Hospital, Paris Cancer Institute CARPEM, AP-HP. Centre, Université Paris Cité, Paris, France.; Department of Children and Adolescents Oncology, Gustave-Roussy Cancer, Paris-Saclay University, Villejuif, France.; Service d'Immunologie et d'Hématologie Pédiatrique, Hôpital Universitaire Robert-Debré, AP-HP, Université Paris Cité, Paris, France.; Department of Paediatric Oncology, Institut d'Haematologie et d'Oncologie Pédiatrique, Centre Léon-Bérard, Lyon, France. Electronic address: [email protected].

DOI: 10.1016/j.bulcan.2024.10.014