Pathogenic ATM mutations occur rarely in a subset of multiple myeloma patients.
Br J Haematol
; 142(6): 925-33, 2008 Sep.
Article
em En
| MEDLINE
| ID: mdl-18573109
ABSTRACT
Ataxia Telangiectasia (A-T) patients have biallelic inactivation of the ATM gene and exhibit a 200-fold-increased frequency of lymphoid tumours. ATM mutations have been found in a number of adult lymphoid malignancies but there is no data on the occurrence of ATM mutations in multiple myeloma tumours. The purpose of our work was to investigate the occurrence of ATM mutations in multiple myeloma and to this end we screened 45 sporadic cases for ATM mutations using denaturing high-performance liquid chromatography analysis and DNA sequencing. Pathogenic ATM mutations were identified in 2/45 of the myelomas compared with a published estimate of ATM mutant allele frequency in the UK population of 2/521 (P = 0.033). One was the missense mutation 7181C>T which was then modelled in an expression system and the S2394L protein shown to have no ATM kinase activity. The second myeloma had the pathogenic ATM splice site mutation IVS40-1G>C leading to loss of exon 41. We also report a 48-year-old ataxia telangiectasia patient who developed multiple myeloma. Taken together our study suggests that ATM mutation may play a role in the pathogenesis of a subset of multiple myelomas.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
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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Mieloma Múltiplo
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Mutação
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Proteínas de Neoplasias
Tipo de estudo:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
Idioma:
En
Revista:
Br J Haematol
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Reino Unido