BRAF Mutations in Thyroid Tumors Are Restricted to Papillary Carcinomas and Anaplastic or Poorly Differentiated Carcinomas Arising from Papillary Carcinomas

Marina N. Nikiforova, Edna T. Kimura, Manoj Gandhi, Paul Williams Biddinger, Jeffrey A. Knauf, Fulvio Basolo, Zhaowen Zhu, Riccardo Giannini, Giuliana Salvatore, Alfredo Fusco, Massimo Santoro, James A. Fagin, Yuri E. Nikiforov

Research output: Contribution to journalArticle

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Abstract

Activating point mutations of the BRAF gene have been recently reported in papillary thyroid carcinomas. In this study, we analyzed 320 thyroid tumors and six anaplastic carcinoma cell lines and detected BRAF mutations in 45 (38%) papillary carcinomas, two (13%) poorly-differentiated carcinomas, three (10%) anaplastic carcinomas, and five (83%) thyroid anaplastic carcinoma cell lines but not in follicular, Hürthle cell, and medullary carcinomas, follicular and Hürthle cell adenomas, or benign hyperplastic nodules. All mutations involved a T→A transversion at nucleotide 1796. In papillary carcinomas, BRAF mutations were associated with older age, classic papillary carcinoma or tall cell variant histology, extrathyroidal extension, and more frequent presentation at stages III and IV. All BRAF-positive poorly differentiated and anaplastic carcinomas contained areas of preexisting papillary carcinoma, and mutation was present in both the well-differentiated and dedifferentiated components. These data indicate that BRAF mutations are restricted to papillary carcinomas and poorly differentiated and anaplastic carcinomas arising from papillary carcinomas. They are associated with distinct phenotypical and biological properties of papillary carcinomas and may participate in progression to poorly differentiated and anaplastic carcinomas.

Original languageEnglish (US)
Pages (from-to)5399-5404
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume88
Issue number11
DOIs
StatePublished - Nov 1 2003
Externally publishedYes

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Papillary Carcinoma
Tumors
Thyroid Gland
Cells
Carcinoma
Mutation
Histology
Neoplasms
Nucleotides
Genes
Cell Line
Medullary Carcinoma
Point Mutation
Adenoma

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

BRAF Mutations in Thyroid Tumors Are Restricted to Papillary Carcinomas and Anaplastic or Poorly Differentiated Carcinomas Arising from Papillary Carcinomas. / Nikiforova, Marina N.; Kimura, Edna T.; Gandhi, Manoj; Biddinger, Paul Williams; Knauf, Jeffrey A.; Basolo, Fulvio; Zhu, Zhaowen; Giannini, Riccardo; Salvatore, Giuliana; Fusco, Alfredo; Santoro, Massimo; Fagin, James A.; Nikiforov, Yuri E.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 88, No. 11, 01.11.2003, p. 5399-5404.

Research output: Contribution to journalArticle

Nikiforova, MN, Kimura, ET, Gandhi, M, Biddinger, PW, Knauf, JA, Basolo, F, Zhu, Z, Giannini, R, Salvatore, G, Fusco, A, Santoro, M, Fagin, JA & Nikiforov, YE 2003, 'BRAF Mutations in Thyroid Tumors Are Restricted to Papillary Carcinomas and Anaplastic or Poorly Differentiated Carcinomas Arising from Papillary Carcinomas', Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 11, pp. 5399-5404. https://doi.org/10.1210/jc.2003-030838
Nikiforova, Marina N. ; Kimura, Edna T. ; Gandhi, Manoj ; Biddinger, Paul Williams ; Knauf, Jeffrey A. ; Basolo, Fulvio ; Zhu, Zhaowen ; Giannini, Riccardo ; Salvatore, Giuliana ; Fusco, Alfredo ; Santoro, Massimo ; Fagin, James A. ; Nikiforov, Yuri E. / BRAF Mutations in Thyroid Tumors Are Restricted to Papillary Carcinomas and Anaplastic or Poorly Differentiated Carcinomas Arising from Papillary Carcinomas. In: Journal of Clinical Endocrinology and Metabolism. 2003 ; Vol. 88, No. 11. pp. 5399-5404.
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abstract = "Activating point mutations of the BRAF gene have been recently reported in papillary thyroid carcinomas. In this study, we analyzed 320 thyroid tumors and six anaplastic carcinoma cell lines and detected BRAF mutations in 45 (38{\%}) papillary carcinomas, two (13{\%}) poorly-differentiated carcinomas, three (10{\%}) anaplastic carcinomas, and five (83{\%}) thyroid anaplastic carcinoma cell lines but not in follicular, H{\"u}rthle cell, and medullary carcinomas, follicular and H{\"u}rthle cell adenomas, or benign hyperplastic nodules. All mutations involved a T→A transversion at nucleotide 1796. In papillary carcinomas, BRAF mutations were associated with older age, classic papillary carcinoma or tall cell variant histology, extrathyroidal extension, and more frequent presentation at stages III and IV. All BRAF-positive poorly differentiated and anaplastic carcinomas contained areas of preexisting papillary carcinoma, and mutation was present in both the well-differentiated and dedifferentiated components. These data indicate that BRAF mutations are restricted to papillary carcinomas and poorly differentiated and anaplastic carcinomas arising from papillary carcinomas. They are associated with distinct phenotypical and biological properties of papillary carcinomas and may participate in progression to poorly differentiated and anaplastic carcinomas.",
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