Two distinct thyroid tumours in a patient with Cowden syndrome carrying both a 10q23 and a mitochondrial DNA germline deletion.
J Med Genet
; 48(11): 779-82, 2011 Nov.
Article
em En
| MEDLINE
| ID: mdl-21926107
ABSTRACT
BACKGROUND:
Cowden syndrome (CS) is an autosomal dominant disorder characterised by macrocephaly, specific mucocutaneous features and predisposition to benign and malignant tumours. Detectable mutations in the PTEN gene account for 80-85% of cases. METHODS/RESULTS:
Here, the authors report a patient with macrocephaly and typical CS mucocutaneous features who developed dysplastic cerebellar gangliocytoma and two synchronous thyroid cancers of papillary and oncocytic type, in whom a germline 500-Kb deletion on chromosome 10q23 including PTEN was detected. Molecular characterisation of thyroid cancer led to the identification of the oncogenic BRAFV600E mutation in the papillary carcinoma. BRAFV600E has been proposed to cause cancer only in the presence of a tumour-suppressor mutation, which, in this case, could be the PTEN deletion. In the oncocytic carcinoma, a large deletion in the mitochondrial-DNA-encoded MTND1 was found, associated with respiratory complex I disassembly, which was subsequently shown to be a constitutional, de novo genetic lesion.CONCLUSIONS:
This is the first reported case of a patient with CS carrying constitutional deletions in both the nuclear and the mitochondrial genome that might help elucidate some aspects of CS pathogenesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome do Hamartoma Múltiplo
/
Neoplasias da Glândula Tireoide
/
Carcinoma
/
Carcinoma Papilar
/
Mutação em Linhagem Germinativa
/
Proteínas Proto-Oncogênicas B-raf
/
PTEN Fosfo-Hidrolase
/
NADH Desidrogenase
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
J Med Genet
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Itália