Bone sarcomas and cancer predisposition syndromes

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.