Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours
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Publication year
2011Source
British Journal of Cancer, 105, 4, (2011), pp. 586-91ISSN
Publication type
Article / Letter to editor
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Organization
Neurology
Paediatrics - OUD tm 2017
Journal title
British Journal of Cancer
Volume
vol. 105
Issue
iss. 4
Page start
p. 586
Page end
p. 91
Subject
DCN 2: Functional Neurogenomics; N4i 4: Auto-immunity, transplantation and immunotherapyAbstract
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.
This item appears in the following Collection(s)
- Academic publications [245263]
- Electronic publications [132514]
- Faculty of Medical Sciences [93208]
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