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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
Mutational analysis of the ARAF gene in human cancers
Jong Woo Lee1, Young Hwa Soung, Su Young Kim
1Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Abstract:
Deregulation of RAS signal transduction has been implicated in the malignant growth of human cancer cells. The BRAF gene, encoding a RAF family member in the downstream pathway of RAS, is somatically mutated in a number of human cancers, raising the possibility that other RAF family members might be mutated in human cancers. In this study we analyzed the genomic DNAs for the detection of somatic mutations of the ARAF gene in 60 human cancer cell lines and 323 primary human cancer tissues, including colorectal carcinomas, gastric carcinomas, ovarian tumors and acute leukemias. The MOLT-4 leukemia cell line was found to harbor an ARAF gene mutation resulting in an amino acid substitution (A451T) at the activation segment in the kinase domain of ARAF. In the cancer tissues we could not detect any ARAF gene mutation. Our data indicate that, in contrast to the BRAF gene, the ARAF gene is rarely mutated in human cancers, and suggest that alterations of the RAS pathway by ARAF gene mutation may not play an important role in the pathogenesis of human cancers.
Insights
The ARAF gene, unlike BRAF, is rarely mutated in human cancers. Researchers found only one mutation in the MOLT-4 leukemia cell line, suggesting ARAF mutations are not a major driver of cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- RAS signal transduction pathway deregulation is crucial in human cancer development.
- BRAF gene mutations are common in various human cancers, prompting investigation into other RAF family members.
Purpose of the Study:
- To investigate the frequency and role of ARAF gene mutations in human cancers.
- To determine if ARAF gene mutations contribute to cancer pathogenesis.
Main Methods:
- Genomic DNA analysis of 60 human cancer cell lines and 323 primary human cancer tissues (colorectal, gastric, ovarian, acute leukemia).
- Somatic mutation detection in the ARAF gene.
Main Results:
- A single ARAF gene mutation (A451T) was identified in the MOLT-4 leukemia cell line.
- No ARAF gene mutations were detected in the analyzed primary human cancer tissues.
Conclusions:
- The ARAF gene is rarely mutated in human cancers, contrasting with BRAF.
- ARAF gene mutations likely play a limited role in the pathogenesis of human cancers compared to other RAS pathway alterations.
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