Issues

Somatic mosaicism, where two or more cell populations have different genotypes, can occur in normal cells as they undergo mutagenesis over an individual's life span. These mosaic variants can arise early in embryogenesis and be present in adult tissues. Mosaicism in cancer susceptibility genes has been observed in individuals with clinical features of hereditary predisposition syndromes, but the contribution of these mosaic variants to the development of apparently sporadic cancers has yet to be defined. Pareja, Ptashkin, Brown, and colleagues analyzed paired tumor/blood sequencing data from over 35,000 unselected patients with cancer and showed that mosaic variants affecting cancer susceptibility genes can occur early in embryogenesis and are likely to contribute to tumorigenesis, thereby increasing the risk for developing cancer. The detection of these variants may ultimately influence clinical decisions as well as preventive measures for patients and their offspring. For more information, see the article by Pareja, Ptashkin, Brown, and colleagues on page 949.