ATM alterations have been reported as germline variants which predispose to inherited cancer syndromes and as somatic (acquired) variants in tumors. ATM is part of many signalling networks, including cell metabolism and growth, oxidative stress, and chromatin remodelling, all of which can affect cancer progression. Although ATM is rightly considered to be a tumour suppressor, ATM signalling can also be advantageous to cancer cells, particularly in resistance to radio- and chemotherapeutic treatment. For this reason, ATM inhibitors have been developed for use in cancer therapy.

ATM alterations have been reported as germline variants which predispose to inherited cancer syndromes and as somatic (acquired) variants in tumors, including breast cancer. ATM is part of many signalling networks, including cell metabolism and growth, oxidative stress, and chromatin remodelling, all of which can affect cancer progression. Although ATM is rightly considered to be a tumour suppressor, ATM signalling can also be advantageous to cancer cells, particularly in resistance to radio- and chemotherapeutic treatment. For this reason, ATM inhibitors have been developed for use in cancer therapy.

ATM is a member of the protein superfamily of phosphatidylinositol 3-kinase related serine/threonine kinases (PIKKs). ATM is part of many signaling networks, including cell metabolism and growth, oxidative stress, and chromatin remodeling, all of which can affect cancer progression. Although ATM is considered to be a tumor suppressor, ATM signaling may be advantageous to cancer cells in some settings, particularly in resistance to radio- and chemotherapeutic treatment. Germline ATM mutations are the defining feature of ataxia telangiectasia syndrome, a rare, neurodegenerative, autosomal disorder. ATM somatic mutations are associated with endometrial, colon, pancreatic, breast cancers and urothelial cancers. ATM-mutant cancers are increasingly sensitive to DNA damaging agents due to deficits in DNA repair pathways, and ATM loss may result in better response to checkpoint inhibition in some cancers. For this reason, the use of ATM inhibitors in cancer therapy is under exploration. Genetic alterations of ATM have been identified in 5% of pancreatic adenocarcinomas. ATM F858L has been identified in the scientific literature, but has not been biochemically characterized and therefore, its effect on ATM protein function is unknown. According to ClinVar, this variant is considered to be a benign/likely benign germline variant (https://preview.ncbi.nlm.nih.gov/clinvar/variation/132736/). Clinical correlation is recommended.

ATM alterations have been reported as germline variants which predispose to inherited cancer syndromes and as somatic (acquired) variants in tumors. ATM is part of many signalling networks, including cell metabolism and growth, oxidative stress, and chromatin remodelling, all of which can affect cancer progression. Although ATM is considered to be a tumour suppressor, ATM signaling may be advantageous to cancer cells in some settings, particularly in resistance to radio- and chemotherapeutic treatment. For this reason, the use of ATM inhibitors in cancer therapy is under exploration.