Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours.
Br J Cancer
; 105(4): 586-91, 2011 Aug 09.
Article
em En
| MEDLINE
| ID: mdl-21792198
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ataxia Telangiectasia
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Proteínas Serina-Treonina Quinases
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Proteínas de Ciclo Celular
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Proteínas Supressoras de Tumor
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Proteínas de Ligação a DNA
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Mutação
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Neoplasias
Limite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
País como assunto:
Europa
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article