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An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
Published on: April 17, 2013
BRAF mutations are not an alternative explanation for the molecular etiology of ras-mutation negative cold thyroid
1Medical Department, University of Leipzig, Leipzig, Germany.
Abstract:
Activation of the RAS/RAF/MEK/ERK/MAP kinase pathway is a known mediator of signaling that results in cellular proliferation. Moreover, this activation can lead to a growth advantage of tumor cells. Therefore, mitogenic mutations in the RAS family of oncogenes are detectable in a significant percentage in most tumors. Moreover, mutations in the BRAF gene have recently been suggested as an alternate predominant cause of colorectal and papillary thyroid cancers without ras mutations. Similar to neoplasms of other organs mutations of all three ras genes can be found in thyroid tumors. In our set of 40 cold thyroid adenoma and adenomatous nodules ras mutations were detected in only a single case. We therefore tested these hypofunctional tumors for BRAF mutations. Genomic DNA was extracted from nodular and surrounding tissue. Mutational hot spots in exons 11 and 15 of the BRAF gene were polymerase chain reaction (PCR) amplified and denaturing gradient gel electrophoresis was used to screen for mutations. No point mutation could be found in the two exons of the BRAF gene. Our study suggests that BRAF mutations are rather rare in solitary cold adenomas and adenomatous nodules and do not explain the molecular etiology of ras mutation-negative cold thyroid nodules.
Insights
RAS/RAF/MEK/ERK/MAP kinase pathway activation drives cell proliferation and tumor growth. This study investigated BRAF mutations in cold thyroid nodules, finding them to be rare and not a primary cause of these tumors.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- The RAS/RAF/MEK/ERK/MAP kinase pathway is crucial for cellular proliferation and tumor growth.
- RAS oncogene mutations are common in various tumors.
- BRAF mutations are implicated in cancers like colorectal and papillary thyroid cancer, particularly in RAS mutation-negative cases.
Purpose of the Study:
- To investigate the prevalence and role of BRAF mutations in solitary cold thyroid adenomas and adenomatous nodules.
- To determine if BRAF mutations contribute to the molecular etiology of RAS mutation-negative cold thyroid nodules.
Main Methods:
- Genomic DNA extraction from nodular and surrounding thyroid tissue.
- Polymerase chain reaction (PCR) amplification of BRAF gene mutational hotspots in exons 11 and 15.
- Screening for mutations using denaturing gradient gel electrophoresis.
Main Results:
- RAS mutations were detected in only one out of 40 cases of cold thyroid adenomas and adenomatous nodules.
- No point mutations were identified in the screened exons (11 and 15) of the BRAF gene.
- BRAF mutations were found to be rare in the studied cohort.
Conclusions:
- BRAF mutations do not appear to be a significant factor in the development of solitary cold adenomas and adenomatous nodules.
- The molecular basis for RAS mutation-negative cold thyroid nodules remains largely unexplained by BRAF mutations.
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