Human Genetics

, Volume 114, Issue 1, pp 118–120 | Cite as

Mutational analysis of BRAF and K-ras in gastric cancers: absence of BRAF mutations in gastric cancers

  • Il-Jin Kim
  • Jae-Hyun Park
  • Hio Chung Kang
  • Yong Shin
  • Hye-Won Park
  • Hye-Rin Park
  • Ja-Lok Ku
  • Seok-Byung Lim
  • Jae-Gahb Park
Short Report

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.

Keywords

Gastric Cancer Papillary Thyroid Carcinoma BRAF Mutation Gastric Cancer Cell Line Gastric Cancer Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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.

References

  1. 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 113:1892–1900PubMedGoogle Scholar
  2. 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 33:367–372Google Scholar
  3. 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 62:6997–7000PubMedGoogle Scholar
  4. 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 95:625–627CrossRefPubMedGoogle Scholar
  5. 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 417:949–954CrossRefPubMedGoogle Scholar
  6. Fenoglio-Preiser CM, Wang J, Stemmermann GN, Noffsinger A (2003) TP53 and gastric carcinoma: a review. Hum Mutat 21:258–270CrossRefPubMedGoogle Scholar
  7. 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 392:402–405CrossRefPubMedGoogle Scholar
  8. 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 86:529–532CrossRefPubMedGoogle Scholar
  9. 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:e97Google Scholar
  10. 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 63:1454–1457PubMedGoogle Scholar
  11. 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 75:2794–2801PubMedGoogle Scholar
  12. 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 33:19–20CrossRefPubMedGoogle Scholar
  13. Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE (2002) Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature 418:934CrossRefPubMedGoogle Scholar
  14. 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 95:484–486CrossRefPubMedGoogle Scholar
  15. 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 17:274–275CrossRefPubMedGoogle Scholar
  16. 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 95:108–113CrossRefPubMedGoogle Scholar
  17. 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 44:177–180Google Scholar
  18. 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 62:6451–6455PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Il-Jin Kim
    • 1
  • Jae-Hyun Park
    • 1
  • Hio Chung Kang
    • 1
  • Yong Shin
    • 1
  • Hye-Won Park
    • 1
  • Hye-Rin Park
    • 1
  • Ja-Lok Ku
    • 1
  • Seok-Byung Lim
    • 2
  • Jae-Gahb Park
    • 1
    • 2
    • 3
  1. 1.Korean Hereditary Tumor Registry, Cancer Research Institute and Cancer Research CenterSeoul National UniversitySeoulKorea
  2. 2.Department of SurgerySeoul National University College of MedicineSeoulKorea
  3. 3.Research Institute and HospitalNational Cancer CenterGyeonggiKorea

Personalised recommendations