Related Experiment Video
Updated: Aug 6, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
No evidence of ARAF, CRAF and MET mutations in BRAFT1799A negative human papillary thyroid carcinoma
Atsushi Kumagai1, Hiroyuki Namba, Shu Takakura
1Department of Molecular Medicine, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagaski, Japan.
Abstract:
The MAPK signaling pathway plays a crucial role in tumorgenesis and cell proliferation in human papillary thyroid carcinoma (PTC). Ret/PTC rearrangements, RAS and BRAF mutations, the main non-overlapping genetic alterations all leading to MAPK cascade activation, are cumulatively identified in 60-80% of PTCs. In approximately one-fourth of the cases, oncogenic background potentially contributing to MAPK activation in PTC might be different. We therefore attempted to evaluate the mutational status of genes encoding other members of RAF family known to act upstream of MAPKs, ARAF and CRAF (RAF-1). In addition we also analyzed the MET gene that encodes hepatocyte growth factor/scatter factor receptor overexpressed in most of PTCs and a MAPK cascade contributor. In 129 Japanese patients with PTC, BRAF(T1799A) was detected in 65 cases (50.4%), and the remaining 64 tumor specimens were subjected to mutation analysis of kinase domains of ARAF, CRAF and MET genes, and hotspots of K- and N-RAS genes. No ARAF, CRAF, MET, K- and N-RAS mutations were revealed. Based on these observations, we concluded that despite the fact that ARAF, CRAF and MET are actively expressed, alterations of these genes are rare in PTC and unlikely to play a perceptible role in the molecular pathogenesis of this type of human malignancy.
Insights
Mutations in ARAF, CRAF, and MET genes are rare in papillary thyroid carcinoma (PTC). These genetic alterations are unlikely to significantly contribute to the molecular pathogenesis of PTC, despite the MAPK pathway
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The MAPK signaling pathway is critical in human papillary thyroid carcinoma (PTC) tumorgenesis and cell proliferation.
- Common genetic alterations like Ret/PTC rearrangements, RAS, and BRAF mutations activate the MAPK cascade in 60-80% of PTC cases.
- Alternative oncogenic pathways may contribute to MAPK activation in a subset of PTCs.
Purpose of the Study:
- To investigate the mutational status of ARAF, CRAF, and MET genes in Japanese PTC patients.
- To evaluate the potential role of ARAF, CRAF, and MET alterations in the molecular pathogenesis of PTC.
- To identify alternative MAPK pathway activation mechanisms beyond known mutations.
Main Methods:
- Analysis of 129 Japanese PTC patient tumor specimens.
- BRAF(T1799A) mutation screening.
- Mutation analysis of kinase domains of ARAF, CRAF, MET, and hotspots of K- and N-RAS genes in remaining samples.
Main Results:
- BRAF(T1799A) mutation was detected in 50.4% of PTC cases.
- No mutations were identified in the ARAF, CRAF, MET, K-RAS, or N-RAS genes in the analyzed PTC specimens.
- Despite active expression, alterations in ARAF, CRAF, and MET are infrequent in PTC.
Conclusions:
- Genetic alterations in ARAF, CRAF, and MET are rare in human papillary thyroid carcinoma.
- These specific gene alterations do not appear to play a significant role in the molecular pathogenesis of PTC.
- The study highlights the importance of BRAF mutations as a primary driver in a significant proportion of PTC cases.
More Related Videos
11:20Simple and Rapid Method to Obtain High-quality Tumor DNA from Clinical-pathological Specimens Using Touch Imprint Cytology
Published on: March 21, 2018
10:16Employing Digital Droplet PCR to Detect BRAF V600E Mutations in Formalin-fixed Paraffin-embedded Reference Standard Cell Lines
Published on: October 8, 2015
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
02:23Abnormal Proliferation