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

Open access
Nikiforova, Marina N., Kimura, Edna T., Gandhi, Manoj, Biddinger, Paul W., Knauf, Jeffrey A., Basolo, Fulvio, Zhu, Zhaowen, Giannini, Riccardo, Salvatore, Giuliana, Fusco, Alfredo, Santoro, Massimo, Fagin, James A., Nikiforov, Yuri E.·2003·The Journal of Clinical Endocrinology & Metabolism

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.

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Citations

Cites

  • Mutations of the BRAF gene in human cancer

    Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674

  • RAF/RAS oncogenes and mismatch-repair status

    Rajagopalan, H., Bardelli, A., Lengauer, C., Kinzler, K. W., Vogelstein, B., & Velculescu, V. E. (2002) · Nature · doi:10.1038/418934a · Cited by 1,224 · cited 1×

    “Nucleotide 1796, the only mutational site in thyroid carcinomas, was the most frequently affected hot spot in other types of human cancers where BRAF is mutated, such as malignant melanoma and colorectal carcinoma (11, 12).”
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Metadata

Authors
Nikiforova, M. N., Kimura, E. T., Gandhi, M., Biddinger, P. W., Knauf, J. A., Basolo, F., Zhu, Z., Giannini, R., Salvatore, G., Fusco, A., Santoro, M., Fagin, J. A., & Nikiforov, Y. E.
Venue
The Journal of Clinical Endocrinology & Metabolism
Published
2003-11-01
Volume
88
Issue
11
Pages
5399-5404
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
OpenAlex
W2104875539
Cited by
1,042
References
2
FWCI
32.53
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: BRAF Mutations in Thyroid Tumors Are Restricted to Papillary Carcinomas and Anaplastic or Poorly Differentiated Carcinomas Arising from Papillary Carcinomas. https://app.cochat.ai/papers/10.1210/jc.2003-030838
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Nikiforova, M. N., Kimura, E. T., Gandhi, M., Biddinger, P. W., Knauf, J. A., Basolo, F., Zhu, Z., Giannini, R., Salvatore, G., Fusco, A., Santoro, M., Fagin, J. A., & Nikiforov, Y. E. (2003). BRAF Mutations in Thyroid Tumors Are Restricted to Papillary Carcinomas and Anaplastic or Poorly Differentiated Carcinomas Arising from Papillary Carcinomas. The Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/jc.2003-030838

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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