TY - JOUR T1 - Atm heterozygosity does not increase tumor susceptibility to ionizing radiation alone or in a p53 heterozygous background. JF - Oncogene Y1 - 2008 A1 - Jiang-Hua Mao A1 - Wu, D A1 - DelRosario, R A1 - Castellanos, A A1 - Balmain, A A1 - Perez-Losada, J KW - Animals KW - Ataxia Telangiectasia Mutated Proteins KW - Cell Cycle Proteins KW - DNA-Binding Proteins KW - Genes, p53 KW - Genes, Tumor Suppressor KW - Genetic Predisposition to Disease KW - Heterozygote KW - Loss of Heterozygosity KW - Mice KW - Mice, Inbred C57BL KW - Mice, Knockout KW - Neoplasms KW - Protein-Serine-Threonine Kinases KW - Radiation Tolerance KW - Radiation, Ionizing KW - Tumor Suppressor Proteins AB -

Ataxia-Telangiectasia (A-T) is an autosomal recessive human disease characterized by genetic instability, radiosensitivity, immunodeficiency and cancer predisposition, because of mutation in both alleles of the ATM (ataxia-telangiectasia mutated) gene. The role of Atm heterozygosity in cancer susceptibility is controversial, in both human and mouse. Earlier studies identified deletions near the Atm gene on mouse chromosome 9 in radiation-induced lymphomas from p53 heterozygous mice. To determine whether Atm was the target of these deletions, Atm heterozygous as well as Atm/P53 double heterozygous mice were treated with ionizing radiation. There were no significant differences in tumor latency, progression and lifespan after gamma-radiation in Atm heterozygous mice compared with their wild-type control counterparts. Deletions were found on chromosome 9 near the Atm locus in radiation-induced tumors, but in 50% of the cases the deletion included the knockout allele, and the expression of Atm was maintained in the tumors indicating that loss of heterozygosity on chromosome 9 is not driven by Atm, but by an alternative tumor suppressor gene located near Atm on this chromosome. We conclude that Atm heterozygosity does not confer an increase in tumor susceptibility in this context.

VL - 27 IS - 51 U1 - http://www.ncbi.nlm.nih.gov/pubmed/18679420?dopt=Abstract ER -