BRAF and KRAS mutations in stomach cancer.
Ras proteins control signaling pathways that are key regulators of several aspects of normal cell growth and malignant transformation. BRAF, which encodes a RAF family member in the downstream pathway of RAS, is somatically mutated in a number of human cancers. The activating mutation of BRAF is known to play a role in tumor development. As there have been no data on the BRAF mutation in stomach cancer, we analysed the genomic DNAs from 319 stomach carcinomas for the detection of somatic mutations of BRAF. Overall, we detected BRAF mutations in seven stomach carcinomas (2.2%). Five of the seven BRAF mutations involved Val 599, the previously identified hotspot, but the substituted amino acid (V599 M) was different from the most common BRAF mutation (V599E). The remaining two mutations involved a conserved amino acid (D593G). One tumor had both BRAF and KRAS mutations. This is the first report on BRAF mutation in stomach cancer, and the data indicate that BRAF is occasionally mutated in stomach cancer, and suggest that alterations of RAS pathway both by RAS and BRAF mutations contribute to the pathogenesis of stomach cancer.
Lee
Sug Hyung
SH
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul 137-701, Korea.
Lee
Jong Woo
JW
Soung
Young Hwa
YH
Kim
Hong Sug
HS
Park
Won Sang
WS
Kim
Su Young
SY
Lee
Jong Heun
JH
Park
Jik Young
JY
Cho
Yong Gu
YG
Kim
Chang Jae
CJ
Nam
Suk Woo
SW
Kim
Sang Ho
SH
Lee
Jung Young
JY
Yoo
Nam Jin
NJ
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002277:Carcinoma / Q000235:genetics; D017124:Conserved Sequence; D015894:Genome, Human; D006801:Humans; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D013274:Stomach Neoplasms / Q000235:genetics*; D014633:Valine / Q000378:metabolism; D018631:ras Proteins
C117307:KRAS protein, human; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D014633:Valine