Abstract
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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Arber N, Shapira I, Ratan J, Stern B, Hibshoosh H, Moshkowitz M, Gammon M, Fabian I and Halpern Z . (2000). Gastroenterology, 118, 1045–1050.
Bae JM, Won YJ, Jung KW, Suh KA, Ahn DH and Park JG . (1999). J. Korean Cancer Assoc., 30, 1175–1183.
Bos JL . (1989). Cancer Res., 49, 4682–4689.
Brose MS, Volpe P, Feldman M, Kumar M, Rishi I, Gerrero R, Einhorn E, Herlyn M, Minna J, Nicholson A, Roth JA, Albelda SM, Davies H, Cox C, Brignell G, Stephens P, Futreal PA, Wooster R, Stratton MR and Weber BL . (2002). Cancer Res., 62, 6997–7000.
Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR and Futreal PA . (2002). Nature, 417, 949–954.
Jiang W, Kahn SM, Guillem JG, Lu SH and Weinstein IB . (1989). Oncogene, 4, 923–928.
Kolch W . (2000). Biochem. J., 351 (Part 2), 289–305.
Lee KH, Lee JS, Suh C, Kim SW, Kim SB, Lee JH, Lee MS, Park MY, Sun HS and Kim SH . (1995). Cancer, 75, 2794–2801.
Naoki K, Chen TH, Richards WG, Sugarbaker DJ and Meyerson M . (2002). Cancer Res., 62, 7001–7003.
Neubauer A, Dodge RK, George SL, Davey FR, Silver RT, Schiffer CA, Mayer RJ, Ball ED, Wurster-Hill D and Bloomfield CD . (1994). Blood, 83, 1603–1611.
Peyssonnaux C and Eychene A . (2001). Biol. Cell, 93, 53–62.
Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, Moses TY, Hostetter G, Wagner U, Kakareka J, Salem G, Pohida T, Heenan P, Duray P, Kallioniemi O, Hayward NK, Trent JM and Meltzer PS . (2003). Nat. Genet., 33, 19–20.
Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B and Velculescu VE . (2002). Nature, 418, 934.
Satyamoorthy K, Li G, Gerrero MR, Brose MS, Volpe P, Weber BL, Van Belle P, Elder DE and Herlyn M . (2003). Cancer Res., 63, 756–759.
Shin MS, Park WS, Kim SY, Kanf SJ, Song KY, Park JY, Dong SM, PiJH, Oh RR, Lee JY, Yoo NJ and Lee SH . (1999). Am. J. Pathol., 154, 1785–1791.
Smith ML, Snaddon J, Neat M, Cambal-Parrales M, Arch R, Lister TA and Fitzgibbon J . (2003). Leukemia, 17, 274–275.
Yuen ST, Davies H, Chan TL, Ho JW, Bignell GR, Cox C, Stephens P, Edkins S, Tsui WW, Chan AS, Futreal PA, Stratton MR, Wooster R and Leung SY . (2002). Cancer Res., 62, 6451–6455.
Acknowledgements
This work was supported by Grant (No. R02-2002-000-00050-0) from the KOSEF.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lee, S., Lee, J., Soung, Y. et al. BRAF and KRAS mutations in stomach cancer. Oncogene 22, 6942–6945 (2003). https://doi.org/10.1038/sj.onc.1206749
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1206749
Keywords
This article is cited by
-
SLC39A10 promotes malignant phenotypes of gastric cancer cells by activating the CK2-mediated MAPK/ERK and PI3K/AKT pathways
Experimental & Molecular Medicine (2023)
-
Mouse models of Kras activation in gastric cancer
Experimental & Molecular Medicine (2022)
-
AIMP2-DX2 provides therapeutic interface to control KRAS-driven tumorigenesis
Nature Communications (2022)
-
Activating KRAS and GNAS mutations in heterotopic submucosal glands of the stomach
Journal of Gastroenterology (2022)
-
KRAS Mutation in Gastric Cancer and Prognostication Associated with Microsatellite Instability Status
Pathology & Oncology Research (2019)