Issues

Of the more than 270,000 breast cancers and 57,000 pancreatic cancers diagnosed annually, approximately 10-15% are hereditary and are associated with a germline pathogenic variant or likely pathogenic variant (PV) in a hereditary cancer risk gene. The ATM (ataxia telangiectasia mutated) gene is located on chromosome 11q22.3 and is comprised of 66 exons that code a 350.6 kDa protein involved in various cellular activities, including DNA double-strand break repair through its activity as a phosphorylase of key proteins involved in response to DNA damage. While the recessively inherited childhood disease Ataxia Telangiectasia requires two (homozygous) ATM PVs to manifest disease and is rare in the population, approximately 1 in 300 individuals carry one (heterozygous) ATM PV. In the study starting on page 433, Hall and colleagues examine the cancer risks in heterozygous ATM PV carriers using a large database of over 600,000 individuals tested with a multi-gene panel for hereditary cancer risk. Elevated risks for several cancers including breast, pancreatic, prostate, and gastric among others were identified in ATM PV carriers. The cover image shows the exons of the human ATM, as well as the PV location on the gene, frequency as represented by the height of the line at each location on the gene, and variant type represented by the color of the line, for the 4,607 ATM PVs identified in the study population.