CHEK2 is a moderate risk cancer predisposition gene, but is currently listed as “Li-Fraumeni syndrome 2” in public resources used by medical geneticists and patients. Li-Fraumeni syndrome experts consider that TP53 is the only gene causing this multi-cancer syndrome. Our comprehensive comparison of phenotypic characteristics of CHEK2 and TP53 carriers undergoing multigene panel testing provides conclusive evidence that none of the phenotypes significantly associated with TP53, including extremely early onset breast cancer and sarcomas, are associated with CHEK2. We hope these empiric findings will promote removal of “Li-Fraumeni syndrome 2” as the disease associated with CHEK2, and avoid potential recommendation of excessive clinical interventions for CHEK2 carriers. (By Dr. Cristina Fortuno, https://jmg.bmj.com/content/early/2023/08/03/jmg-2023-109464 )

Dr. Cristina Fortuno