CHEK2is not a Li-Fraumeni syndrome gene: time to update public resources

Abstract

The gene-disease relationship forCHEK2remains listed as ‘Li-Fraumeni syndrome 2’ in public resources such as OMIM and MONDO, despite published evidence to the contrary, causing frustration among Li-Fraumeni syndrome (LFS) clinical experts. Here, we compared personal cancer characteristics of 2095CHEK2and 248TP53pathogenic variant carriers undergoing multigene panel testing at Ambry Genetics against 15 135 individuals with no known pathogenic variant. Our results from a within-cohort logistic regression approach highlight obvious differences between clinical presentation ofTP53andCHEK2pathogenic variant carriers, with no evidence ofCHEK2being associated with any of theTP53-related core LFS cancers. These findings emphasise the need to replace ‘Li-Fraumeni syndrome 2’ as theCHEK2-associated disease name, thereby limiting potential confusion.