Evaluation of a Four-Gene Panel for Hereditary Cancer Risk Assessment (original) (raw)

BRCA1/2 are tumor suppressor genes involved in DNA double-strand break repair. They are the most penetrant genes for hereditary breast and ovarian cancers, but pathogenic variants in these two genes can be identified only in a fraction of hereditary cases. Following the diffusion of BRCA molecular testing and the availability of specific therapeutic strategies for the management of pathogenic variant carriers, the demand for the analysis of additional predisposing genetic factors has increased. Indeed, there is accumulating evidence regarding the role of other genes, including CHEK2 and PALB2. Both of them are involved in the same molecular pathway as BRCA genes, with CHEK2 being responsible for cell cycle stopping to allow the repair of DNA double-strand breaks and PALB2 being able to interact with BRCA1 and activate BRCA2. Thus, their role as additional hereditary cancer predisposing factors is intriguing. Accordingly, guidelines for hereditary cancer risk assessment have been upd...