Instead, the mutation patterns of the tumour suppressor TP53 (which encodes p53), ataxia telangiectasia mutated (ATM) and cyclin-dependent kinase inhibitor 2A (CDKN2A; which encodes p16INK4A and p14ARF) support the oncogene-induced DNA replication stress model, which attributes genomic instability and TP53 and ATM mutations to oncogene-induced DNA damage.
<i>Atm</i>-mutant rats (<i>Atm<sup>L2262P/L2262P</sup></i> ) expressed low levels of ATM protein, suggesting a destabilizing effect of the mutation, and had a significantly reduced lifespan compared with <i>Atm<sup>+/+</sup></i> Whereas these rats did not show cerebellar atrophy, they succumbed to hind-limb paralysis (45%), and the remainder developed tumors.
Tumors with ATM mutations only partially correlated with tumors with loss of an ATM allele through an 11q deletion and, interestingly, those 11q-deleted tumors with a second wild-type ATM allele had a preserved DNA damage response.
SETD2-mutated LUADs exhibited relatively poor recurrence- free survival (RFS) and mutations in STK11 and ATM were associated with poor RFS among KRAS-mutant tumors.
The ATM gene was shown to sustain frequent loss-of-function mutations in T-PLL tumor cells, consistent with functioning as a tumor suppressor gene in this leukemia.
We compared the potential effect of the ATM gene mutation and cell behavior including cell-cycle arrest and induction of apoptosis in the tumor cell lines MGC803 and BGC823 with and without ionizing radiation (IR) exposure.
Regarding qualitative imaging features, on univariate analysis, tumor location was significantly associated with APC (p = 0.032) and RASA1 mutation (p = 0.032); CRM status was significantly associated with ATM mutation (p = 0.021); and lymph node metastasis was significantly associated with BRCA2 (p = 0.046) mutation.
In patients with aldosterone-producing adenomas either responsive or unresponsive to the renin-angiotensin system, no differences were detected using SSCP analysis in the coding region of the AT1 receptor gene in peripheral blood or tumour tissue.
Our aim was to determine if CLL tumors with a chromosome 11q deletion might be divided into two subgroups based on the status of the remaining ATM allele.
These findings indicate that ATM gene mutations in MCL are mainly truncating or missense mutations involving the PI-3K domain, and that may play a role in the pathogenesis of a subset of these tumors with increased numbers of chromosomal imbalances.
Germ-line mutations in the ataxia-telangiectasia mutated (ATM) and CHK2 genes have been detected in patients with mantle cell lymphoma (MCL), suggesting a potential role of these genes in genetic predisposition to these tumors.
Targeted sequencing analysis of the tumor identified a somatic frame-shift mutation in ATM, a gene known to be associated with radio-sensitivity in the germline.
Furthermore, genistein decreased DNA methylation in the promoter region of multiple tumor suppressor genes (TSGs) such as ataxia telangiectasia mutated (ATM), adenomatous polyposis coli (APC), phosphatase and tensin homolog (PTEN), mammary serpin peptidase inhibitor (SERPINB5), and increased the mRNA expression of these genes.
The strong predisposition of AT patients to develop T-PLL and the high frequency of T-cell leukemias/lymphomas observed in atm-deficient mice, together with the known functions of the ATM protein, led us to evaluate the ATM gene as a potential tumor suppressor gene involved in T-PLL.
An analysis of the relationship between the presence of a novel ATM mutation and either patient demographics or tumor properties demonstrated a significant difference between African Americans (3/7 = 43%) and other ethnic groups (3/45 = 7%, P = 0.026).
We analyzed the clinical outcome of breast cancer patients carrying sequence variants in the ATM gene who received postoperative radiotherapy after breast conservative surgery to test whether an increased cellular radiosensitivity may translate into enhanced tumor cell killing and thereby result in an improvement of the therapeutic ratio.
Following the classical tumor suppressor inactivation scheme, tumors showing loss of heterozygosity (LOH) at the ATM locus should present an increased proportion of mutated ATM forms.
To evaluate the role of constitutive epigenetic changes in normal body cells of BRCA1/BRCA2-mutation negative patients, we have developed a deep bisulfite sequencing assay targeting the promoter regions of 8 tumor suppressor (TS) genes (BRCA1, BRCA2, RAD51C, ATM, PTEN, TP53, MLH1, RB1) and the estrogene receptor gene (ESR1), which plays a role in tumor progression.
Mutations in the ATM gene located on the long arm of chromosome 11 at 11q22-23 cause ataxia-telangiectasia, an autosomal recessive disorder that is associated with increased incidence of malignancy and, particularly, lymphoid tumors.