Expression status of ataxia-telangiectasia-mutated gene correlated with prognosis in advanced gastric cancer

Are DNA Repair Factors Promising Biomarkers for Personalized Therapy in Gastric Cancer?

“…Our data are also consistent with a recent study by Kang et al, who investigated ATM in 70 gastric cancers and demonstrated that low levels of ATM correlated to poor differentiation, lymph node metastasis, and poor 5-year survival (4). Taken together, the data, including ours, suggest that loss of ATM expression may be an important prognostic marker in gastric cancer.…”

Tumor protein D52 represents a negative regulator of ATM protein levels

“…ATM is frequently altered in hematological cancers, where T-cell prolymphocytic leukemia, B-cell chronic lymphocytic leukemia, and mantle cell lymphoma are all characterized by high rates of inactivating mutations, and/or deletion of ATM. 38 Reduced ATM protein levels have also been reported in breast cancer, 39 glioblastoma, 40 gastric cancer, 41 and colorectal cancer, 42 yet the cellular mechanisms that lead to deregulation of ATM expression are poorly understood. In sporadic breast cancer, although loss of heterozygosity (LOH) in the region of ATM on chromosome 11q22.3 has been reported in up to 40% cases, somatic mutations of ATM are infrequent.…”

Low ATM protein expression and depletion of p53 correlates with olaparib sensitivity in gastric cancer cell lines

“…Consequently, ATM has been proposed to be an independent prognostic 12 and a predictive marker for individual therapy in advanced gastric cancer patients. 13 The clinical significance of disrupted DNA repair pathways lies in the potential exploitation of synthetic lethality, best exemplified by the preferential toxicity of small-molecule PARP-1 inhibitors in BRCA-deficient tumors. 14,15 Similar synthetic lethal interactions have been demonstrated between PARP inhibitors and a number of other genes related to DNA repair and the DNA damage response, including ATM.…”

“…ATM deficiency has been reported in up to 60% of gastric cancer and is associated with poor prognosis. 13 Like many other malignancies, gastric cancer also displays a high rate of p53 mutation. 25 Therefore, we hypothesized that a significant fraction of gastric cancer cases might benefit from treatment with PARP-1 inhibitor, either with or without ATM inhibitor.…”