Clinical Features and Treatment Strategies of Li-Fraumeni Syndrome Patients With Inherited TP53 Mutations

Li-Fraumeni syndrome is a rare autosomal dominant disorder caused by a pathogenic mutation of the tumor suppressor gene TP53. This disease starts at an early age and has been shown to be associated with multiple tumors. The study aims to discuss the clinical and genetic characteristics of Li-Fraumeni syndrome (LFS) and to provide therapeutic experience of LFS.

We conducted a retrospective analysis of the clinicopathologic features, family history, treatment and follow-up in five LFS patients with germline TP53 (NCBI Gene: 7157, HGNC: 11998, OMIM: 191170) pathogenic/likely pathogenic (P/LP) variants. This research had been approved by the ethics committee and implemented.

Our study involved five LFS patients with germline TP53 P/LP variants, including thyroid cancer, ovarian melanoma, colon cancer, fibrosarcoma, and lung cancer. Among this group of patients, the age at which tumors first appeared was between 24 and 53 years old. Three patients had a family history of tumors, and the other two were probands in the family. Traditional chemotherapy has limited effectiveness in clinical practice and may increase the risk of tumor development. However, immune checkpoint inhibitors (ICIs) have shown unexpected efficacy in patients with high programmed cell death ligand-1 (PD-L1) expression. Next-generation sequencing (NGS) and PD-L1 detection may provide more potential targets for LFS patients to achieve better therapeutic outcomes. In addition, we have added a new TP53 frameshift mutation spectrum, namely c.642_643delTA (p.H214Qfs*7), which belongs to the pathogenic variant. This mutant has not been described in the existing literature.

Patients with LFS may be potential beneficiaries of immune checkpoint inhibitors and targeted therapies.