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.
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Comprehensive TCGA PanCanAtlas (https://gdc.cancer.gov/about-data/publications/pancanatlas)
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