Abstract
Recently, BRAF mutations were found in a variety of human cancers. Interestingly, the most common of BRAF mutation (V599E) has not been identified in tumors with K-ras mutations. Whereas the majority of human cancer types has been screened for BRAF mutations, no detailed studies on gastric cancers have been investigated. Thus, we decided to investigate the incidence of BRAF mutations in gastric cancers, and the relationship between BRAF and K-ras mutations in such cancers. Three non-pathogenic BRAF polymorphisms and seven K-ras missense mutations were found in 66 gastric cancers and 16 gastric cancer cell lines. Although only 9% of our gastric cancer panels had K-ras mutations, the incidence of BRAF mutations was not high. Thus, BRAF mutations, which are present in a variety of other human cancers, do not seem to be involved in gastric cancer development.
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References
Arber N, Han EK, Sgambato A, Piazza GA, Delohery TM, Begemann M, Weghorst CM, Kim NH, Pamukcu R, Ahnen DJ, Reed JC, Weinstein IB, Holt PR (1997) A K-ras oncogene increases resistance to sulindac-induced apoptosis in rat enterocytes. Gastroenterology 113:1892–1900
Bae JM, Won YJ, Jung KW, Suh KA, Ahn DH, Park JG (2001) Annual report of the central cancer registry in Korea—1999: based on registered data from 128 hospitals. Cancer Res Treat 33:367–372
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, Weber BL (2002) BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res 62:6997–7000
Cohen Y, Xing M, Mambo E, Guo Z, Wu G, Trink B, Beller U, Westra WH, Ladenson PW, Sidransky D (2003) BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst 95:625–627
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, Futreal PA (2002) Mutations of the BRAF gene in human cancer. Nature 417:949–954
Fenoglio-Preiser CM, Wang J, Stemmermann GN, Noffsinger A (2003) TP53 and gastric carcinoma: a review. Hum Mutat 21:258–270
Guilford P, Hopkins J, Harraway J, McLeod M, McLeod N, Harawira P, Taite H, Scoular R, Miller A, Reeve AE (1998) E-cadherin germline mutations in familial gastric cancer. Nature 392:402–405
Kim I-J, Ku J-L, Yoon K-A, Heo S-C, Jeong S-Y, Choi H-S, Hong K-H, Yang S-K, Park J-G (2000) Germline mutations of the dpc4 gene in Korean juvenile polyposis patients. Int J Cancer 86:529–532
Kim I-J, Park J-H, Kang H-C, Shin Y, Lim S-B, Ku J-L, Yang H-K, Lee K-U, Park J-G (2003) A novel germline mutation in the MET extracellular domain in a Korean patient with the diffuse type of familial gastric cancer. J Med Genet 40:e97
Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA (2003) High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res 63:1454–1457
Lee KH, Lee JS, Suh C, Kim SW, Kim SB, Lee JH, Lee MS, Park MY, Sun HS, Kim SH (1995) Clinicopathologic significance of the K-ras gene codon 12 point mutation in stomach cancer. An analysis of 140 cases. Cancer 75:2794–2801
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, Meltzer PS (2003) High frequency of BRAF mutations in nevi. Nat Genet 33:19–20
Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE (2002) Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature 418:934
Singer G, Oldt R 3rd, Cohen Y, Wang BG, Sidransky D, Kurman RJ, Shih IEM (2003) Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J Natl Cancer Inst 95:484–486
Smith ML, Snaddon J, Neat M, Cambal-Parrales M, Arch R, Lister TA, Fitzgibbon J (2003) Mutation of BRAF is uncommon in AML FAB type M1 and M2. Leukemia 17:274–275
Woo DK, Kim HS, Lee HS, Kang YH, Yang HK, Kim WH (2001) Altered expression and mutation of beta-catenin gene in gastric carcinomas and cell lines. Int J Cancer 95:108–113
Yoon K-A, Ku J-L, Yang H-K, Kim W-H, Park S-Y, Park J-G (1999) Germline mutations of E-cadherin gene in Korean familial gastric cancer patients. J Hum Genet 44:177–180
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, Leung SY (2002) Similarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasia. Cancer Res 62:6451–6455
Acknowledgements
This work was supported by a research grant from the National Cancer Center, Korea. I.-J. Kim, J.-H. Park, H.C. Kang, and Y. Shin were supported by the BK21 project for Medicine, Dentistry, and Pharmacy.
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Kim, IJ., Park, JH., Kang, H.C. et al. Mutational analysis of BRAF and K-ras in gastric cancers: absence of BRAF mutations in gastric cancers. Hum Genet 114, 118–120 (2003). https://doi.org/10.1007/s00439-003-1027-0
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DOI: https://doi.org/10.1007/s00439-003-1027-0