title: Classical point mutations of RET, BRAF and RAS oncogenes are not shared in papillary and medullary thyroid cancer occurring simultaneously in the same gland.
abstract: BACKGROUND
  Papillary (PTC) and medullary (MTC) thyroid carcinomas represent two distinct entities, but quite frequently, they may occur simultaneously.
  
  
  OBJECTIVE
  To provide genetic analysis of PTC and MTC occurring in the same patient (PTC/MTC) to elucidate their origin.
  
  
  METHODS
  Sequencing analysis of RAS, BRAF and RET oncogenes hot spots mutations in tumoral and normal tissues of 24 PTC/MTC patients.
  
  
  RESULTS
  Two of 24 patients (8.3 %) were affected by familial MTC (FMTC) harboring RET germline mutations in all tissues. Eight of 22 (36.4 %) sporadic cases did not show any somatic mutation in the three tissue components. Considering the MTC component, 10/22 (45.4 %) patients did not show any somatic mutation, 7 of 22 (31.8 %) harbored the M918T RET somatic mutation and 4/22 (18.2 %) presented mutations in the H-RAS gene. In an additional case (1/22, 4.6 %), H-RAS and RET mutations were simultaneously present. Considering the PTC component, 1 of 24 (4.2 %) patients harbored the V600E BRAF mutation, 1 of 24 (4.2 %) the T58A H-RAS mutation and 1 of 24 (4.2 %) the M1T K-RAS mutation, while the remaining PTC cases did not show any somatic mutation. In one case, the MTC harbored a RET mutation and the PTC a BRAF mutation. None of the mutations found were present in both tumors.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study analyzing a possible involvement of RET, BRAF and RAS oncogene mutations in PTC/MTC. These data clearly suggest that the classical activating mutations of the oncogenes commonly involved in the pathogenesis of PTC and MTC may not be responsible for their simultaneous occurrence.
authors.affiliation: Department of Clinical and Experimental Medicine (Endocrine Unit), Univesity-Hospital of Pisa, Pisa, Italy. ciampirf1@hotmail.com.
authors.forename: R
authors.initials: R
authors.lastname: Ciampi
authors.affiliation: Department of Clinical and Experimental Medicine (Endocrine Unit), Univesity-Hospital of Pisa, Pisa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Romei
authors.affiliation: Department of Clinical and Experimental Medicine (Endocrine Unit), Univesity-Hospital of Pisa, Pisa, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pieruzzi
authors.affiliation: Department of Clinical and Experimental Medicine (Endocrine Unit), Univesity-Hospital of Pisa, Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Tacito
authors.affiliation: Department of Clinical and Experimental Medicine (Endocrine Unit), Univesity-Hospital of Pisa, Pisa, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Molinaro
authors.affiliation: Department of Clinical and Experimental Medicine (Endocrine Unit), Univesity-Hospital of Pisa, Pisa, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Agate
authors.affiliation: Department of Clinical and Experimental Medicine (Endocrine Unit), Univesity-Hospital of Pisa, Pisa, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Bottici
authors.affiliation: Department of Clinical and Experimental Medicine (Endocrine Unit), Univesity-Hospital of Pisa, Pisa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Casella
authors.affiliation: Department of Surgical, Medical and Molecular Pathology and Critical Care, University-Hospital of Pisa, Pisa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Ugolini
authors.affiliation: Department of Surgical, Medical and Molecular Pathology and Critical Care, University-Hospital of Pisa, Pisa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Materazzi
authors.affiliation: Department of Surgical, Medical and Molecular Pathology and Critical Care, University-Hospital of Pisa, Pisa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Basolo
authors.affiliation: Department of Clinical and Experimental Medicine (Endocrine Unit), Univesity-Hospital of Pisa, Pisa, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Elisei
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D018276:Carcinoma, Medullary / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins
keywords: Medullary thyroid carcinoma; Molecular biology; Papillary thyroid carcinoma; Simultaneous tumors