Mutational analysis of the ARAF gene in human cancers.
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.
Lee
Jong Woo
JW
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Soung
Young Hwa
YH
Kim
Su Young
SY
Park
Won Sang
WS
Nam
Suk Woo
SW
Min
Woo Sung
WS
Kim
Sang Ho
SH
Lee
Jung Young
JY
Yoo
Nam Jin
NJ
Lee
Sug Hyung
SH
D004247:DNA; D004252:DNA Mutational Analysis; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D048490:raf Kinases / Q000235:genetics* / Q000378:metabolism
D004247:DNA; D048490:raf Kinases