Germline deletion and a somatic mutation of the PRKAR1A gene in a Carney complex-related pituitary adenoma.
Eur J Endocrinol
; 172(1): K5-10, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25336503
ABSTRACT
OBJECTIVE:
The objective was to assess involvement of loss of the PRKAR1A gene encoding a type 1α regulatory subunit of cAMP-dependent protein kinase A located on 17q24 in a Carney complex (CNC)-related pituitary adenoma.DESIGN:
We investigated aberrations of the PRKAR1A gene in a CNC patient with a GH-producing pituitary adenoma, whose family has three other members with probable CNC.METHODS:
A gene mutation was identified by a standard DNA sequencing method based on PCR. DNA copy number was measured to evaluate allelic loss on 17q24 by quantitative PCR. The breakpoints of deletion were determined by cloning a rearranged region in the deleted allele.RESULTS:
A PRKAR1A mutation of c.751_758del8 (p.S251LfsX16) was found in genomic DNA obtained from a pituitary adenoma, but not leukocytes from the patient. Reduced DNA copy number at loci including the PRKAR1A gene on 17q24 was detected in both the tumor and leukocytes, suggesting a deletion at the loci at the germline level. The deletion size was determined to be â¼ 0.5 Mb and this large deletion was also found in two other family members.CONCLUSION:
This is the first case showing a CNC-related pituitary adenoma with the combination of somatic mutation and a large inherited deletion of the PRKAR1A gene. Biallelic inactivation of PRKAR1A appears to be necessary for the development of CNC-related pituitary adenoma.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Hipofisárias
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Adenoma
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Deleção de Genes
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Mutação em Linhagem Germinativa
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Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico
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Complexo de Carney
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Eur J Endocrinol
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article