The ataxia telangiectasia mutated (ATM) gene is important in the cellular response to DNA double stranded breaks. ATM genetic abnormalities include deletions and mutations which may occur alone or together. ATM mutations have been reported to occur in approximately 35% of chronic lymphocytic leukemia; biallelic ATM inactivation (deletions and mutations) are associated with a poor outcome in some setttings compared to monoallelic ATM deletion or mutation in CLL. The ATM mutations occur throughout the gene and are putative loss of function variants (missense, nonsense and frameshift mutations). ATM mutations have also been reported in other types of lymphoma including mantle cell lymphoma (50%) and T cell prolymphocytic leukemia (46%).

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.

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.

This gene is a known cancer gene.

This gene is a known cancer gene.

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. Genetic alterations in ATM have been reported in ~15% of urothelial carcinomas. However, the significance of this particular variant (R2443Q) is unknown, according to ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/142211/)

ATM is a member of the protein superfamily of phosphatidylinositol 3-kinase related serine/threonine kinases (PIKKs). ATM functions as a tumor suppressor that initiates DNA damage checkpoint signaling. Germline loss-of-function mutations in ATM have been identified in the autosomal recessive disorder Ataxia telangiectasia. Somatic mutations in ATM have been identified in lymphoid malignancies and a selection of solid tumors. 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. Genetic alterations of ATM have been identified in approximately 10% of lung adenocarcinomas. One study predicted impaired ATM kinase activity in the setting of ATM R2691C mutation based on structural modeling; however, these results have not been validated biochemically. Of note, this variant is reported in ClinVar as a germline variant of uncertain significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/133636/). Correlation with other clinical and lab findings is recommended.

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.