Activating BRAF gene mutations are uncommon in hormone refractory prostate cancer in Caucasian patients

Köllermann,J.; Albrecht,H.; Schlomm,T.; Huland,H.; Graefen,M.; Bokemeyer,C.; Simon,R.; Sauter,G.; Wilczak,W.

doi:10.3892/ol_00000127

Activating BRAF gene mutations are uncommon in hormone refractory prostate cancer in Caucasian patients

Authors:
- J. Köllermann
- H. Albrecht
- T. Schlomm
- H. Huland
- M. Graefen
- C. Bokemeyer
- R. Simon
- G. Sauter
- W. Wilczak
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Affiliations: Institute of Pathology, Hubertus Wald Tumorzentrum, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany
Published online on: July 1, 2010 https://doi.org/10.3892/ol_00000127
Pages: 729-732

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Abstract

Activating mutations in the cytosolic serine/threonine kinase, BRAF, have been reported in a variety of neoplasms. BRAF activation may contribute to tumor growth via activation of the MAP/ERK kinase pathway, and BRAF represents a possible therapeutic target. Activating BRAF mutations were recently reported in approximately 10% of prostate cancer cases in Asian patients. In the present study, 43 hormone refractory prostate cancers were analyzed for BRAF mutations in order to determine whether anti-BRAF therapy is a suitable approach for advanced prostate cancer patients. In all of the studied tumors, BRAF exons 11 and 15 were PCR-amplified and sequenced, including the backward and forward sequences. BRAF mutations were noted only in the positive control tissues, but were not found in any of the 43 analyzed prostate cancers. We conclude that BRAF mutations occur only rarely in prostate cancers in Caucasian patients and are not associated with tumor progression. The application of anti-BRAF therapies may therefore not be beneficial for prostate cancer.

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1	Jemal A, Murray T, Ward E, et al: Cancer statistics, 2005. CA Cancer J Clin. 1:10–30. 2005. View Article : Google Scholar
2	Cohen Y, Xing M, Mambo E, et al: BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst. 8:625–627. 2003. View Article : Google Scholar : PubMed/NCBI
3	Wilhelm SM, Carter C, Tang L, et al: BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 19:7099–7109. 2004. View Article : Google Scholar : PubMed/NCBI
4	Preto A, Goncalves J, Rebocho AP, et al: Proliferation and survival molecules implicated in the inhibition of BRAF pathway in thyroid cancer cells harbouring different genetic mutations. BMC Cancer. 1:3872009. View Article : Google Scholar
5	Cho NY, Choi M, Kim BH, Cho YM, Moon KC and Kang GH: BRAF and KRAS mutations in prostatic adenocarcinoma. Int J Cancer. 8:1858–1862. 2006. View Article : Google Scholar : PubMed/NCBI
6	Chong H, Vikis HG and Guan KL: Mechanisms of regulating the Raf kinase family. Cell Signal. 5:463–469. 2003. View Article : Google Scholar : PubMed/NCBI
7	Davies H, Dicks E, Stephens P, et al: High throughput DNA sequence variant detection by conformation sensitive capillary electrophoresis and automated peak comparison. Genomics. 3:427–432. 2006. View Article : Google Scholar : PubMed/NCBI
8	Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE and Fagin JA: 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. 7:1454–1457. 2003.PubMed/NCBI
9	Honecker F, Wermann H, Mayer F, et al: Microsatellite instability, mismatch repair deficiency, and BRAF mutation in treatment-resistant germ cell tumors. J Clin Oncol. 13:2129–2136. 2009. View Article : Google Scholar : PubMed/NCBI
10	Bamford S, Dawson E, Forbes S, Clements J, Pettett R, Dogan A, Flanagan A, Teague J, Futreal PA, Stratton MR and Wooster R: The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website. Br J Cancer. 91:355–358. 2004.PubMed/NCBI
11	Wan PT, Garnett MJ, Roe SM, Lee S, Niculescu-Duvaz D, Good VM, Jones CM, Marshall CJ, Springer CJ, Barford D and Marais R: Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell. 116:855–867. 2004. View Article : Google Scholar : PubMed/NCBI
12	Hoeflich KP, Gray DC, Eby MT, et al: Oncogenic BRAF is required for tumor growth and maintenance in melanoma models. Cancer Res. 2:999–1006. 2006. View Article : Google Scholar : PubMed/NCBI
13	Sumimoto H, Miyagishi M, Miyoshi H, et al: Inhibition of growth and invasive ability of melanoma by inactivation of mutated BRAF with lentivirus-mediated RNA interference. Oncogene. 36:6031–6039. 2004. View Article : Google Scholar : PubMed/NCBI
14	Pratilas CA and Solit DB: Therapeutic strategies for targeting BRAF in human cancer. Rev Recent Clin Trials. 2:121–134. 2007. View Article : Google Scholar : PubMed/NCBI
15	Gao H, Ouyang X, Banach-Petrosky WA, Gerald WL, Shen MM and Abate-Shen C: Combinatorial activities of Akt and B-Raf/Erk signaling in a mouse model of androgen-independent prostate cancer. Proc Natl Acad Sci USA. 39:14477–14482. 2006. View Article : Google Scholar : PubMed/NCBI
16	Jeong JH, Wang Z, Guimaraes AS, et al: BRAF activation initiates but does not maintain invasive prostate adenocarcinoma. PLoS One. 12:e39492008. View Article : Google Scholar : PubMed/NCBI
17	Liu T, Willmore-Payne C, Layfield LJ and Holden JA: Lack of BRAF activating mutations in prostate adenocarcinoma: a study of 93 cases. Appl Immunohistochem Mol Morphol. 2:121–125. 2009. View Article : Google Scholar : PubMed/NCBI
18	Riely GJ, Politi KA, Miller VA and Pao W: Update on epidermal growth factor receptor mutations in non-small cell lung cancer. Clin Cancer Res. 24:7232–7241. 2006. View Article : Google Scholar : PubMed/NCBI
19	Al-Kuraya K, Schraml P, Sheikh S, et al: Predominance of high-grade pathway in breast cancer development of Middle East women. Mod Pathol. 7:891–897. 2005. View Article : Google Scholar : PubMed/NCBI
20	Choi DH, Shin DB, Lee MH, et al: A comparison of five immunohistochemical biomarkers and HER-2/neu gene amplification by fluorescence in situ hybridization in white and Korean patients with early-onset breast carcinoma. Cancer. 8:1587–1595. 2003. View Article : Google Scholar : PubMed/NCBI
21	Michaloglou C, Vredeveld LC, Mooi WJ and Peeper DS: BRAF(E600) in benign and malignant human tumours. Oncogene. 7:877–895. 2008. View Article : Google Scholar : PubMed/NCBI
22	Marchetti A, Felicioni L and Buttitta F: Assessing EGFR mutations. N Engl J Med. 5:526–528. 2006.PubMed/NCBI