Given available evidence that ATM haploinsufficiency can increase cancer risk, we predict that the observed copy number loss has likely contributed to hereditary cancer in this family.
High ATM expression helps DNA repair mechanisms to maintain the cells in the OPMD stage, but low ATM expression causes DNA damage accumulation to increase cell malignancy.
We also discovered 23 novel mutations in NRAS, PIK3CA, SOX9, APC, SMAD4, MSH3, MSH4, PMS1 PMS2, AXIN2, ERBB2, PIK3R1, TGFBR2, and ATM that were not reported in the COSMIC, The Cancer Genome Atlas, and dbSNP databases.
Accumulating evidence has suggested that the ataxia telangiectasia group D complementing (ATDC) gene is an emerging cancer-related gene in multiple human cancer types.
ATM mutations carriers were significantly more likely to have a family history of breast and/or ovarian cancer (26.7% in carriers vs. 8.6% in non-carriers, p < 0.001), as well as a family history of any cancer (60.0% in carriers vs. 31.5% in non-carriers, p = 0.001).
Compared with 51 patients with classic A-T from the Dutch cohort, patients with <i>ATM</i> c.3576G>A had a longer survival and were less likely to develop cancer, respiratory disease or immunodeficiency.
Loss of one or both alleles of ATM results in an increased risk of cancer development, particularly haematopoietic cancer and breast cancer in both humans and mouse models.
Inhibition of ATM and ATR signaling contributes to the efficiency of virus replication and may provide one explanation for the cancer selectivity of cell death induced by the expression of E4orf4 alone.
Germline DNA from 1054 BRCA-mutation-negative Hispanic women with hereditary BC (BC diagnosed at age <51 years, bilateral BC, breast and ovarian cancer, or BC diagnosed at ages 51-70 years with ≥2 first-degree or second-degree relatives who had BC diagnosed at age <70 years), 312 local controls, and 887 multiethnic cohort controls was sequenced and analyzed for 12 known and suspected, high-penetrance and moderate-penetrance cancer susceptibility genes (ataxia telangiectasia mutated [ATM], breast cancer 1 interacting protein C-terminal helicase 1 [BRIP1], cadherin 1 [CDH1], checkpoint kinase 2 [CHEK2], nibrin [NBN], neurofibromatosis type 1 [NF1], partner and localizer of BRCA2 [PALB2], phosphatase and tensin homolog [PTEN], RAD51 paralog 3 [RAD51C], RAD51D, serine/threonine kinase 11 [STK11], and TP53).
Mutations in the ATM gene result in a condition known as ataxia-telangiectasia (A-T) that is characterized by cancer predisposition, radiosensitivity, neurodegeneration, sterility, and acquired immune deficiency.
Our work shows that oxidized ATM-mediated glycolysis enhancement in hypoxic stromal fibroblasts plays an essential role in cancer cell invasion and metastasis and may implicate oxidized ATM as a target for breast tumor treatment.
Not only AT patients, but also certain ATM heterozygous mutation carriers show a significantly reduced life expectancy due to cancer and ischemic heart disease; in particular, female carriers having particular alleles have an increased risk of breast cancer.
Ataxia-telangiectasia (A-T), an autosomal recessive disorder characterized by progressive neurologic dysfunction, oculocutaneous telangiectasia, immunodeficiency, and cancer susceptibility, is caused by mutations in the ATM gene.
Mutations in the ATM gene cause dysfunction in cell-cycle, apoptosis and V (D) J recombination leading to neurodegeneration, cellular, humoral immunodeficiencies and predisposition to malignancies.
Although ATM is involved in the DNA damage response, ATM-associated tumours are distinct from BRCA1-associated tumours in terms of morphological characteristics and genomic alterations, and they are also distinguishable from sporadic breast tumours, thus opening up the possibility to identify ATM variant carriers outside the ataxia-telangiectasia disorder and direct them towards effective cancer risk management and therapeutic strategies.
A better understanding of the regulation of EBV latency could be harnessed in the conception of novel therapeutic strategies in AT and more generally in all ATM deficient EBV-related malignancies.
The cell cycle checkpoint proteins ataxia-telangiectasia-mutated-and-Rad3-related kinase (ATR) and its major downstream effector checkpoint kinase 1 (CHK1) prevent the entry of cells with damaged or incompletely replicated DNA into mitosis when the cells are challenged by DNA damaging agents, such as radiation therapy (RT) or chemotherapeutic drugs, that are the major modalities to treat cancer.