Molecular Biology Reports

, Volume 39, Issue 2, pp 1595–1599 | Cite as

Combined point mutations in codon 12 and 13 of KRAS oncogene in prostate carcinomas

  • Fatma Silan
  • Yener Gultekin
  • Sinem Atik
  • Davran Kilinc
  • Cabir Alan
  • Fazilet Yildiz
  • Ahmet Uludag
  • Ozturk Ozdemir


Prostate cancer is a common malignancy that develops by structural mutation(s) and/or other genetic alterations in specific genes.The G to T transversions in codon 12 and C to T transitions in codon 13 of KRAS proto-oncogene are predominant point mutations that occur in about 20% of different cancers in human. In the current study it was aimed to investigate the prevalence and predictive significance of KRAS mutations in patients with prostate carcinomas. In a total of 30 fresh tumoural tissue specimens were investigated in patients with prostate carcinoma. All tumoural specimens were histo-pathologically diagnosed and genotyped for codon 12, 13 KRAS point mutations by reverse hybridisation and direct sequencing methods. KRAS mutations were found in 12 (40%) samples with 29 samples deriving from adenocarcinomas and 1 sample was small cell prostate carcinoma. In 1 (3.44%) sample codon 12 was found to be mutated and in 2 (6.8%) samples codon 13 and in 9 (31%) samples combined codon 12 and 13 were found to be mutated particularly in higher grade of tumoural tissues. Our study, based on representative collection of human prostate tumours, indicates that combined mutations in codons 12 and 13 KRAS are relatively infrequent and most commonly occur in prostate carcinomas.


Prostate carcinoma Combined point mutation KRAS proto-oncogene Codon 12 and 13 


Conflict of interest

There is no conflict of interest that could be perceived as prejudicing the impartiality of the current results.


  1. 1.
    Cooner WH, Mosley BR, Rutherford CL Jr, Beard JH, Pond HS, Terry WJ et al (2002) Prostate cancer detection in a clinical urological practice by ultrasonography, digital rectal examination and prostate specific antigen. J Urol 167(2 Pt 2):966–973PubMedGoogle Scholar
  2. 2.
    Eisenberg ML, Park Y, Brinton LA, Hollenbeck AR, Schatzkin A (2010) Fatherhood and incident prostate cancer in a prospective US cohort. Int J Epidemiol. [Epub ahead of print]Google Scholar
  3. 3.
    Heidenreich A, Bellmunt J, Bolla M, Joniau S, Mason M, Matveev V,et,al. (2010) EAU Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Treatment of Clinically Localised Disease. Eur Urol. [Epub ahead of print]Google Scholar
  4. 4.
    Catalona WJ, Richie JP, Ahmann FR, Hudson MA, Scardino PT, Flanigan RC et al (1994) Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: results of a multicenter clinical trial of 6,630 men. J Urol 151(5):1283–1290PubMedGoogle Scholar
  5. 5.
    Damber JE, Aus G (2008) Prostate cancer. Lancet 371(9625):1710–1721PubMedGoogle Scholar
  6. 6.
    Ma CG, Ye DW, Yao XD, Zhang SL, Dai B, Zhang HL et al. (2010) The survival analysis of metastatic prostate cancer. Zhonghua Wai Ke Za Zhi. (15):1166–1169Google Scholar
  7. 7.
    Jimeno A, Messersmith WA, Hirsch FR, Franklin WA, Eckhardt SG (2009) KRAS mutations and sensitivity to epidermal growth factor receptor inhibitors in colorectal cancer: practical application of patient selection. J Clin Oncol 27(7):1130–1136PubMedGoogle Scholar
  8. 8.
    Chen J, Huang XF, Katsifis A (2010) Activation of signal pathways and the resistance to anti-EGFR treatment in colorectal cancer. J Cell Biochem 111(5):1082–1086PubMedGoogle Scholar
  9. 9.
    Mariani P, Lae M, Degeorges A, Cacheux W, Lappartient E, Margogne A et al (2010) Concordant analysis of KRAS status in primary colon carcinoma and matched metastasis. Anticancer Res 30(10):4229–4235PubMedGoogle Scholar
  10. 10.
    Shen Y, Lu Y, Yin X, Zhu G, Zhu J (2010) KRAS and BRAF mutations in prostate carcinomas of Chinese patients. Cancer Genet Cytogenet 198(1):35–39PubMedGoogle Scholar
  11. 11.
    Van Krieken JH, Jung A, Kirchner T, Carneiro F, Seruca R, Bosman FT et al (2008) KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program. Virchows Arch 453(5):417–431PubMedGoogle Scholar
  12. 12.
    de Launay D, Vreijling J, Hartkamp LM, Karpus ON, Abreu JR, van Maanen MA et al (2010) Silencing the expression of Ras family GTPase homologues decreases ınflammation and joint destruction in experimental arthritis. Am J Pathol 177(6):3010–3024PubMedGoogle Scholar
  13. 13.
    Okayama N, Nishioka M, Hazama S, Sakai K, Suehiro Y, Maekawa M et al (2011) The ımportance of evaluation of DNA amplificability in KRAS mutation testing with dideoxy sequencing using formalin-fixed and paraffin-embedded colorectal cancer tissues. Jpn J Clin Oncol 41(2):165–171PubMedGoogle Scholar
  14. 14.
    Singh D, Febbo PG, Ross K, Jackson DG, Manola J, Ladd C et al (2002) Gene expression correlates of clinical prostate cancer behavior. Cancer Cell 1(2):203–209PubMedGoogle Scholar
  15. 15.
    Arslan S, Dogan T, Koksal B, Yıldırım ME, Gumus C, Elagoz S, Akkurt I, Ozdemir O (2008) Tumoral tissue specific promoter hypermethylation of distinct tumor suppressor genes in a case with non-small cell lung carcinoma: a case report. Lung India 25:148–151PubMedGoogle Scholar
  16. 16.
    Fine SW, Gopalan A, Leversha MA, Al-Ahmadie HA, Tickoo SK, Zhou Q et al (2010) TMPRSS2-ERG gene fusion is associated with low Gleason scores and not with high-grade morphological features. Mod Pathol 23(10):1325–1333PubMedGoogle Scholar
  17. 17.
    Bratt O, Garmo H, Adolfsson J, Bill-Axelson A, Holmberg L, Lambe M et al (2010) Effects of prostate-specific antigen testing on familial prostate cancer risk estimates. J Natl Cancer Inst 102(17):1336–1343PubMedGoogle Scholar
  18. 18.
    Pergolizzi RG, Kreis W, Rottach C, Susin M, Broome JD (1993) Mutational status of codons 12 and 13 of the N- and K-ras genes in tissue and cell lines derived from primary and metastatic prostate carcinomas. Cancer Invest 11(1):25–32PubMedGoogle Scholar
  19. 19.
    Shibata D, Capella G, Perucho M (1990) Mutational activation of the c-K-ras gene in human pancreatic carcinoma. Baillieres Clin Gastroenterol 4(1):151–169PubMedGoogle Scholar
  20. 20.
    Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K et al (1989) Mutations in the p53 gene occur in diverse human tumour types. Nature 342(6250):705–708PubMedGoogle Scholar
  21. 21.
    Tartaglia M, Gelb BD (2010) Disorders of dysregulated signal traffic through the RAS-MAPK pathway: phenotypic spectrum and molecular mechanisms. Ann N Y Acad Sci 1214:99–121PubMedGoogle Scholar
  22. 22.
    Capella G, Cronauer-Mitra S, Peinado MA, Perucho M (1991) Frequency and spectrum of mutations at codons 12 and 13 of the C-K-ras gene in human tumors. Environ Health Perspect 93:125–131PubMedGoogle Scholar
  23. 23.
    Watanabe M, Shiraishi T, Yatani R, Nomura AM, Stemmermann GN (1994) International comparison on ras gene mutations in latent prostate carcinoma. Int J Cancer 58(2):174–178PubMedGoogle Scholar
  24. 24.
    Shen MM, Abate-Shen C (2010) Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev 24(18):1967–2000PubMedGoogle Scholar
  25. 25.
    Gallagher DJ, Feifer A, Coleman JA (2010) Genitourinary cancer predisposition syndromes. Hematol Oncol Clin North Am 24(5):861–883PubMedGoogle Scholar
  26. 26.
    Schulz WA, Hoffmann MJ (2009) Epigenetic mechanisms in the biology of prostate cancer. Semin Cancer Biol 12:172–180Google Scholar
  27. 27.
    Konishi N, Hiasa Y, Tsuzuki T, Tao M, Enomoto T, Miller GJ (1997) Comparison of ras activation in prostate carcinoma in Japanese and American men. Prostate 30(1):53–57PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Fatma Silan
    • 1
  • Yener Gultekin
    • 2
  • Sinem Atik
    • 1
  • Davran Kilinc
    • 2
  • Cabir Alan
    • 3
  • Fazilet Yildiz
    • 4
  • Ahmet Uludag
    • 1
  • Ozturk Ozdemir
    • 1
    • 4
  1. 1.Department of Medical Genetics, Faculty of MedicineCanakkale Onsekiz Mart UniversityCanakkaleTurkey
  2. 2.Department of Urology, Faculty of MedicineCumhuriyet UniversitySivasTurkey
  3. 3.Department of Urology, Faculty of MedicineCanakkale Onsekiz Mart UniversityCanakkaleTurkey
  4. 4.Department of Medical Genetics, Faculty of MedicineCumhuriyet UniversitySivasTurkey

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