In conclusion, A-T patients with no ATM kinase activity had a markedly more severe immunological phenotype than those expressing low levels of ATM activity.
Finally, there are reduced expression of the R1 subunit of RR and tissue-specific alterations of mtDNA copy number in ATM null mouse tissues, the latter being recapitulated in tissues from human A-T patients.
Recently, large epidemiological and molecular studies have finally provided conclusive evidence that ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles.
The results demonstrate that ATM mutations that cause ataxia-telangiectasia in biallelic carriers are breast cancer susceptibility alleles in monoallelic carriers, with an estimated relative risk of 2.37 (95% confidence interval (c.i.)= 1.51-3.78, P = 0.0003).
In this study, A-T patients from 16 Russian families were assessed for immunological status and ATM haplotype analysis, and screened for ATM mutations.
This mini-review will summarize the recently published data concerning the ATM gene in sporadic lymphoid malignancies and will discuss the apparent paradox between the predominance of nonsense mutations observed in patient with ataxia-telangiectasia and the high proportion of missense alterations found in sporadic lymphoid tumours.
Ataxia-telangiectasia (A-T) is a syndrome of cancer susceptibility, immune dysfunction, and neurodegeneration that is caused by mutations in the A-T-mutated (ATM) gene.
An exceptionally mild A-T phenotype occurs as a result of homozygosity for the 5762ins137 mutation because of relative preservation of ATM protein expression/kinase activity.
ATM and the catalytic subunit of DNA-dependent protein kinase activate NF-kappaB through a common MEK/extracellular signal-regulated kinase/p90(rsk) signaling pathway in response to distinct forms of DNA damage.
Understanding ATM's mode of action provides new insights into the association between defective responses to DNA damage and cancer, and brings us closer to resolving the issue of cancer predisposition in some A-T carriers.