Notably, no individuals with confirmed germline or likely germline TP53 PVs met classic Li-Fraumeni syndrome (LFS) criteria, only 41% met Chompret LFS criteria, and 59% met neither criteria, based upon provider-reported personal and family cancer history.
Recently, the functional MIR605 variant rs2043556 (A>G) has been identified as a novel LFS phenotype modifier in families with germline TP53 DNA binding variants.
Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disorder associated with TP53 germline mutations and an increased lifetime risk of multiple primary cancers (MPC).
This enabled successful estimation of TP53 penetrance for three LFS cancer types: breast (BR), sarcoma (SA), and others (OT), from 186 pediatric sarcoma families collected at MD Anderson Cancer Center.
In this cohort of patients with LFS enriched in TP53p.R337H pathogenic variant, the incidence of RIMs after treatment of localized breast cancer was lower than previous literature.
However, the prevalence of other tumors of the Li-Fraumeni syndrome (LFS) and Li-Fraumeni-like syndrome (LFL) spectrum, the clinical outcomes and the potential tumor occurrence in relatives carrying this distinct TP53 mutation were not fully investigated.
Questionnaire data were collected for 152 women with confirmed germline TP53 variants enrolled in the National Cancer Institute's LFS study (NCT01443468); of which, 85 had breast cancer, confirmed by pathology/medical reports.
For PV carriers in high-penetrance genes like BRCA1, BRCA2, and TP53, prophylactic mastectomy is often recommended and radiation therapy avoided when possible for those with Li-Fraumeni syndrome (LFS).
Comprehensive approaches are needed to better understand the interplay of germline TP53 variant classification, prevalence estimates, cancer penetrance, and LFS-associated phenotype.
Epidermal growth factor receptor (EGFR) mutation-driven lung cancer is a rare occurrence in patients with Li-Fraumeni syndrome (LFS) characterized by germline mutations in the tumor protein 53 (TP53) gene.
Li-Fraumeni syndrome (LFS), due to TP53 germline mutations, is characterised by a remarkably high incidence of multiple primary cancers (MPCs), and the key role of p53 in response to DNA damage questions the contribution of anticancer treatments to MPCs development.