Promoter methylation is not associated with FLCN irregulation in lung cyst lesions of primary spontaneous pneumothorax.
Mol Med Rep
; 12(5): 7770-6, 2015 Nov.
Article
en En
| MEDLINE
| ID: mdl-26398834
Germline mutations in FLCN are responsible for ~10% of patients with primary spontaneous pneumothorax (PSP), characterized by multiple lung cysts in the middle/lower lobes and recurrent pneumothorax. These clinical features are also observed in a substantial portion of patients with sporadic PSP exhibiting no FLCN coding mutations. To assess the potential underlying mechanisms, 71 patients with PSP were selected, including 69 sporadic and 2 familial cases, who bared FLCN mutationlike lung cysts, however, harbored no FLCN proteinaltering mutations. Notably, in a significant proportion of the patients, FLCN irregulation was observed at the transcript and protein levels. Genetic analyses of the cisregulatory region of FLCN were performed by sequencing and multiplex ligationdependent probe amplification assay. No inheritable DNA defect was detected, with the exception of a heterozygous deletion spanning the FLCN promoter, which was identified in a family with PSP. This mutation caused a reduction in the expression of FLCN in the lung cysts. Pedigree analysis demonstrated that haploinsufficiency of FLCN was pathogenic. To determine whether epigenetic mechanisms may be involved in the irregulation of FLCN, the promoter methylation status was measured in the remainder of the patients. No evidence of FLCN promoter methylation was demonstrated. The present study suggested that FLCN irregulation in lung cysts of PSP is not associated with promoter methylation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neumotórax
/
Proteínas Proto-Oncogénicas
/
Proteínas Supresoras de Tumor
/
Pulmón
Tipo de estudio:
Risk_factors_studies
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
Mol Med Rep
Año:
2015
Tipo del documento:
Article
Pais de publicación:
Grecia