TP53 variants

Variants in TP53 are the most common germline alterations associated with osteosarcoma. Variants in this gene are found in approximately 70% of patients with Li-Fraumeni syndrome (LFS), which is associated with increased risk of osteosarcoma, breast cancer, various brain cancers, soft tissue sarcomas, and other cancers. While rhabdomyosarcoma is the most common sarcoma arising in patients aged 5 years and younger with TP53-associated LFS, osteosarcoma is the most common sarcoma in children and adolescents aged 6 to 19 years.[11] One study observed a high frequency of young patients (age <30 years) with osteosarcoma carrying a known LFS-associated or likely LFS-associated TP53 variant (3.8%) or rare exonic TP53 variant (5.7%), with an overall TP53 variant frequency of 9.5%.[12] Other groups have reported lower rates (3%–7%) of TP53 germline variants in patients with osteosarcoma.[10,13,14]