Detection and molecular characterization of a novel BRAF activated domain mutation in follicular variant of papillary thyroid carcinoma
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Published on: October 8, 2015
Libero Santarpia1, Steven I Sherman, Anna Marabotti
1Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, USA.
Abstract:
To assess the mutational status of BRAF in FVPTC, we directly sequenced the genomic DNA of 30 primary FVPTC samples. BRAF mutations were found in only 4 (13%) tumors. We also identified a previously unknown (novel) mutation in the activation kinase domain of the BRAF (A598V), replacing alanine with valine. Functional analysis showed that this mutation led to the up-regulation of the BRAF kinase activity and its downstream signaling factors. The effect of this mutation on the structural formation of the protein is highlighted. Our results confirm the infrequency of BRAF (V600E) mutation in FVPTC and identify a novel (A598V) mutation of this gene.
Insights
BRAF mutations are rare in follicular variant papillary thyroid carcinoma (FVPTC). Researchers discovered a novel BRAF (A598V) mutation, which increases BRAF kinase activity and downstream signaling.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Follicular variant papillary thyroid carcinoma (FVPTC) is a common subtype of thyroid cancer.
- The BRAF gene is frequently mutated in various cancers, including papillary thyroid carcinoma, but its role in FVPTC is less understood.
Purpose of the Study:
- To investigate the mutational status of the BRAF gene in primary FVPTC samples.
- To identify and characterize any novel BRAF mutations in FVPTC.
Main Methods:
- Direct sequencing of genomic DNA from 30 primary FVPTC samples.
- Functional analysis to assess the impact of identified mutations on BRAF kinase activity and signaling pathways.
- Structural analysis to understand the effect of mutations on protein formation.
Main Results:
- BRAF mutations were detected in only 4 (13%) of the 30 FVPTC samples.
- A novel BRAF mutation, A598V, was identified in the activation kinase domain.
- The novel A598V mutation was shown to up-regulate BRAF kinase activity and downstream signaling.
- The study highlighted the structural implications of the A598V mutation on the BRAF protein.
Conclusions:
- The common BRAF (V600E) mutation is infrequent in FVPTC.
- A novel BRAF (A598V) mutation represents a potential driver in a subset of FVPTC.
- Understanding these mutations can inform targeted therapies for FVPTC.
