title: Analysis of somatic mutations in BRAF, CDKN2A/p16 and PI3KCA in patients with medullary thyroid carcinoma.
abstract: Medullary thyroid carcinoma (MTC), a neuroendocrine tumor originating from thyroid parafollicular cells, has been demonstrated to be associated with mutations in RET, HRAS, KRAS and NRAS. However, the role of other genes involved in the oncogenesis of neural crest tumors remains to be fully investigated in MTC. The current study aimed to investigate the presence of somatic mutations in BRAF, CDKN2A and PI3KCA in MTC, and to investigate the correlation with disease progression. DNA was isolated from paraffin‑embedded tumors and blood samples from patients with MTC, and the hotspot somatic mutations were sequenced. A total of 2 novel HRAS mutations, p.Asp33Asn and p.His94Tyr, and polymorphisms within the 3' untranslated region (UTR) of CDKN2A (rs11515 and rs3088440) were identified, however, no mutations were observed in other genes. It was suggested that somatic point mutations in BRAF, CDKN2A and PI3KCA do not participate in the oncogenesis of MTC. Further studies are required in order to clarify the contribution of the polymorphisms identified in the 3'UTR of CDKN2A in MTC.
authors.affiliation: Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo 04039‑032, Brazil.
authors.forename: Fabrício P
authors.initials: FP
authors.lastname: Nascimento
authors.affiliation: Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo 04039‑032, Brazil.
authors.forename: Mirian G
authors.initials: MG
authors.lastname: Cardoso
authors.affiliation: Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo 04039‑032, Brazil.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Lindsey
authors.affiliation: Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo 04039‑032, Brazil.
authors.forename: Ilda S
authors.initials: IS
authors.lastname: Kunii
authors.affiliation: Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo 04039‑032, Brazil.
authors.forename: Flávia O F
authors.initials: FO
authors.lastname: Valente
authors.affiliation: Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo 04039‑032, Brazil.
authors.forename: Marina M L
authors.initials: MM
authors.lastname: Kizys
authors.affiliation: Department of Pathology, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo 04039‑032, Brazil.
authors.forename: Rosana
authors.initials: R
authors.lastname: Delcelo
authors.affiliation: Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo 04039‑032, Brazil.
authors.forename: Cléber P
authors.initials: CP
authors.lastname: Camacho
authors.affiliation: Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo 04039‑032, Brazil.
authors.forename: Rui M B
authors.initials: RM
authors.lastname: Maciel
authors.affiliation: Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo 04039‑032, Brazil.
authors.forename: Magnus R
authors.initials: MR
authors.lastname: Dias-Da-Silva
mesh_terms: D001483:Base Sequence; D018278:Carcinoma, Neuroendocrine / Q000235:genetics* / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D009687:Nuclear Proteins; C503859:PI3KCA protein, human; D014157:Transcription Factors; D048493:Proto-Oncogene Proteins B-raf