The ATM/p53 pathway is commonly targeted for inactivation in squamous cell carcinoma of the head and neck (SCCHN) by multiple molecular mechanisms

Optimal primer design using the novel primer design program: MSPprimer provides accurate methylation analysis of the ATM promoter

“…Third, bisulfite sequencing data support the notion that at least some primary breast and head and neck tumors (Bolt et al, 2005) show methylation of the ATM promoter. However, these data are in direct contradiction with the extent of methylation demonstrated using MSP for these tumor samples .…”

“…In lymphoid malignancies, inactivating mutations and genetic deletion of the ATM locus are associated with poor prognosis (Austen et al, 2005). Silencing of ATM by promoter hypermethylation has been described in several studies (Ai et al, 2004;Vo et al, 2004;Bolt et al, 2005;Safar et al, 2005;Roy et al, 2006). It has been linked to favorable prognosis in Figure 2 PCRs with the primer pairs detailed in Table 1 were analysed.…”

“…However, all studies reporting ATM methylation used MSP with either the 'Vo' Bolt et al, 2005) or 'Ai' (Ai et al, 2004;Safar et al, 2005;Roy et al, 2006) primers. Studies that analysed the ATM promoter either by bisulfite sequencing or by MSP using different primers failed to detect methylation in breast cancer (Allinen et al, 2002), adult (Luo et al, 1998;Gronbaek et al, 2002) or pediatric lymphoid malignancies (Gumy-Pause et al, 2006).…”

The mTOR pathway negatively controls ATM by up-regulating miRNAs

“…MYCN protein levels are elevated in many xenografts derived from rhabdomyosarcoma and neuroblastoma, but also in atypical teratoid rhabdoid tumors (ATRT), glioblastoma, and ependymoma, and to a lesser extent in osteosarcoma and Ewing sarcoma; therefore, overexpression of MYCN and suppression of ATM expression may have relevance to many childhood solid tumors. The relationship between MYCN overexpression and ATM is not absolute, suggesting that factors other than miR-18a and miR-421 may be involved, such as promoter hypermethylation (42,43). The role of ATM in the initiation or progression of childhood solid tumors has not been studied extensively; however undetectable levels of ATM were reported in 7 of 17 (41%) rhabdomyosarcoma samples (44).…”

Three Epstein–Barr virus latency proteins independently promote genomic instability by inducing DNA damage, inhibiting DNA repair and inactivating cell cycle checkpoints

“…Loss of ATM in the inherited ataxia-telangiectasia syndrome, leads to an increased risk of cancer and hypersensitivity to ionizing radiation (Taylor et al, 1996). Reduced or absent ATM expression, resulting either from deletion of the ATM locus at chromosome 11q23 (Eclache et al, 2004) or methylation of the ATM promoter (Bolt et al, 2005), has been reported in a variety of tumors. Our finding that LMP-1 inhibits ATM expression is in line with the reported loss of Genomic instability in EBV-infected cells B Gruhne et al ATM in EBV-carrying tumors that express latency II such as NPC and HD (Bose et al, 2009).…”