1. Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours.
- Author
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Reiman, A., Srinivasan, V., Barone, G., Last, J. I., Wootton, L. L., Davies, E. G., Verhagen, M. M., Willemsen, M. A., Weemaes, C. M., Byrd, P. J., Izatt, L., Easton, D. F., Thompson, D. J., and Taylor, A. M.
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ATAXIA telangiectasia , *LYMPHOMAS , *BREAST cancer , *CHROMOSOME abnormalities , *BRAIN tumors , *BREAST tumors , *COMPARATIVE studies , *IMMUNOBLOTTING , *RESEARCH methodology , *MEDICAL cooperation , *GENETIC mutation , *PROTEIN kinases , *PROTEINS , *RESEARCH , *RESEARCH funding , *TRANSFERASES , *TUMORS , *DNA-binding proteins , *EVALUATION research , *KAPLAN-Meier estimator , *CELL cycle proteins , *PREVENTION ,BREAST tumor prevention ,TUMOR prevention - Abstract
Background: Immunodeficiency in ataxia telangiectasia (A-T) is less severe in patients expressing some mutant or normal ATM kinase activity. We, therefore, determined whether expression of residual ATM kinase activity also protected against tumour development in A-T.Methods: From a total of 296 consecutive genetically confirmed A-T patients from the British Isles and the Netherlands, we identified 66 patients who developed a malignant tumour; 47 lymphoid tumours and 19 non-lymphoid tumours were diagnosed. We determined their ATM mutations, and whether cells from these patients expressed any ATM with residual ATM kinase activity.Results: In childhood, total absence of ATM kinase activity was associated, almost exclusively, with development of lymphoid tumours. There was an overwhelming preponderance of tumours in patients <16 years without kinase activity compared with those with some residual activity, consistent with a substantial protective effect of residual ATM kinase activity against tumour development in childhood. In addition, the presence of eight breast cancers in A-T patients, a 30-fold increased risk, establishes breast cancer as part of the A-T phenotype.Conclusion: Overall, a spectrum of tumour types is associated with A-T, consistent with involvement of ATM in different mechanisms of tumour formation. Tumour type was influenced by ATM allelic heterogeneity, residual ATM kinase activity and age. [ABSTRACT FROM AUTHOR]- Published
- 2011
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