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Updated: Jun 26, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Aberrant BRAF splicing as an alternative mechanism for oncogenic B-Raf activation in thyroid carcinoma

Essa Y Baitei1, Minjing Zou, Futwan Al-Mohanna

  • 1Department of Genetics, King Faisal Specialist Hospital and Research Centre, PO Box 3354, Riyadh 11211, Saudi Arabia.

The Journal of Pathology
|January 22, 2009
PubMed

Insights

Activating BRAF mutations and novel BRAF splicing variants were found in thyroid cancers. These variants, lacking an inhibitory domain, promote tumor growth and are linked to advanced disease stages.

Area of Science:

  • Oncogenic signaling pathways
  • Molecular oncology
  • Cancer genetics

Background:

  • Activating BRAF mutations are common in papillary thyroid carcinomas (PTCs).
  • The role of aberrant BRAF splicing in thyroid cancer remains unclear.

Purpose of the Study:

  • To investigate aberrant BRAF splicing in thyroid tumors.
  • To determine the association between BRAF splicing variants and BRAF mutations.

Main Methods:

  • Analysis of BRAF splicing and mutations in 68 thyroid tumors.
  • Detection of BRAF(V600E) mutation and novel BRAF splicing variants.
  • Functional studies in cell lines and animal models.

Main Results:

  • BRAF(V600E) mutation found in 20/43 PTCs and 3/3 anaplastic thyroid carcinomas (ATCs).
  • Novel BRAF splicing variants identified in PTCs, FVPTCs, ATCs, and cell lines.
  • Variants associated with advanced disease stage and BRAF(V600E) mutation (p < 0.001).
  • Variants activated MAP kinase pathway, induced cell transformation, and tumor formation in vivo.

Conclusions:

  • Aberrant BRAF splicing variants represent an alternative oncogenic activation mechanism.
  • These variants contribute to thyroid cancer progression, particularly in advanced stages.
  • Combined BRAF(V600E) mutation and splicing variants may drive progression to poorly differentiated thyroid carcinoma.

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