title: Two distinct thyroid tumours in a patient with Cowden syndrome carrying both a 10q23 and a mitochondrial DNA germline deletion.
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.
  
  
  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.
authors.affiliation: Dipartimento di Scienze Ginecologiche, Ostetriche e Pediatriche-Unità Operativa di Genetica Medica, Università di Bologna-Policlinico S.Orsola-Malpighi, Via Massarenti, Bologna, Italy.
authors.forename: Laura Maria
authors.initials: LM
authors.lastname: Pradella
authors.forename: Roberta
authors.initials: R
authors.lastname: Zuntini
authors.forename: Pamela
authors.initials: P
authors.lastname: Magini
authors.forename: Claudio
authors.initials: C
authors.lastname: Ceccarelli
authors.forename: Iria
authors.initials: I
authors.lastname: Neri
authors.forename: Serenella
authors.initials: S
authors.lastname: Cerasoli
authors.forename: Claudio
authors.initials: C
authors.lastname: Graziano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gasparre
authors.forename: Daniela
authors.initials: D
authors.lastname: Turchetti
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000150:complications / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000150:complications / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002879:Chromosomes, Human, Pair 10; D004252:DNA Mutational Analysis; D018095:Germ-Line Mutation; D006223:Hamartoma Syndrome, Multiple / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000235:genetics*; D024862:Oxyphil Cells / Q000378:metabolism / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000150:complications / Q000235:genetics*
chemical_list: D009245:NADH Dehydrogenase; D051059:PTEN Phosphohydrolase; D048493:Proto-Oncogene Proteins B-raf; C482119:BRAF protein, human; C494929:PTEN protein, human; C515075:NADH dehydrogenase subunit 1, human