Atm heterozygosity does not increase tumor susceptibility to ionizing radiation alone or in a p53 heterozygous background

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 suscep...

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Vydáno v:	Oncogene Ročník 27; číslo 51; s. 6596 - 6600
Hlavní autoři:	Mao, J H, Wu, D, DelRosario, R, Castellanos, A, Balmain, A, Perez-Losada, J
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 30.10.2008 Nature Publishing Group
Témata:	Alleles Animals Apoptosis Ataxia Ataxia telangiectasia Ataxia telangiectasia mutated protein Ataxia Telangiectasia Mutated Proteins Biological and medical sciences Cancer Cell Biology Cell Cycle Proteins - genetics Cell Cycle Proteins - physiology Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Chromosome 9 Chromosomes Complications and side effects DNA-Binding Proteins - genetics DNA-Binding Proteins - physiology Fundamental and applied biological sciences. Psychology Gene deletion Genes, p53 Genes, Tumor Suppressor - physiology Genetic aspects Genetic disorders Genetic Predisposition to Disease Genomic instability Health aspects Hematologic and hematopoietic diseases Heterozygosity Heterozygote Human Genetics Immunodeficiency Internal Medicine Ionizing radiation Latency Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Life span Loss of heterozygosity Loss of Heterozygosity - physiology Lymphoma Medical sciences Medicine Medicine & Public Health Mice Mice, Inbred C57BL Mice, Knockout Molecular and cellular biology Mutation Neoplasms - genetics Neoplasms - radiotherapy Oncology p53 Protein Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - physiology Radiation Radiation Tolerance - genetics Radiation, Ionizing Radiosensitivity Risk factors Rodents short-communication Tumor suppressor genes Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - physiology Tumors γ Radiation United States Ataxia-Telangiectasia genetic-background loss-of-heterozygosity lymphoma Skin disease Cardiovascular disease Background noise Carcinogenesis Vascular disease Ionizing radiation TP53 Gene Lymphoproliferative syndrome Tumor Tumor suppressor gene Immunopathology Nervous system diseases Malignant hemopathy Lymphoma Genetic disease Heterozygosity P53 Eye disease Loss of heterozygosity Ataxia telangiectasia ATM/Atm Cancer
ISSN:	0950-9232, 1476-5594, 1476-5594
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Shrnutí:	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 γ-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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0950-9232 1476-5594 1476-5594
DOI:	10.1038/onc.2008.280