Asian Pacific Journal of Cancer Prevention

  • 제13권11호
  • /
  • Pages.5599-5603
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  • 2012
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  • 1513-7368(pISSN)
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  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
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Mutational Analysis of Key EGFR Pathway Genes in Chinese Breast Cancer Patients

  • Tong, Lin (Breast Center Nanfang Hospital, Southern Medical University) ;
  • Yang, Xue-Xi (School of Biotechnology, Southern Medical University) ;
  • Liu, Min-Feng (Breast Center Nanfang Hospital, Southern Medical University) ;
  • Yao, Guang-Yu (Breast Center Nanfang Hospital, Southern Medical University) ;
  • Dong, Jian-Yu (Breast Center Nanfang Hospital, Southern Medical University) ;
  • Ye, Chang-Sheng (Breast Center Nanfang Hospital, Southern Medical University) ;
  • Li, Ming (School of Biotechnology, Southern Medical University)
  • 발행 : 2012.11.30
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초록

Background: The epidermal growth factor receptor (EGFR) is a potential therapeutic target for breast cancer treatment; however, its use does not lead to a marked clinical response. Studies of non-small cell lung cancer and colorectal cancer showed that mutations of genes in the PIK3CA/AKT and RAS/RAF/MEK pathways, two major signalling cascades downstream of EGFR, might predict resistance to EGFR-targeted agents. Therefore, we examined the frequencies of mutations in these key EGFR pathway genes in Chinese breast cancer patients. Methods: We used a high-throughput mass-spectrometric based cancer gene mutation profiling platform to detect 22 mutations of the PIK3CA, AKT1, BRAF, EGFR, HRAS, and KRAS genes in 120 Chinese women with breast cancer. Results: Thirteen mutations were detected in 12 (10%) of the samples, all of which were invasive ductal carcinomas (two stage I, six stage II, three stage III, and one stage IV). These included one mutation (0.83%) in the EGFR gene (rs121913445-rs121913432), three (2.50%) in the KRAS gene (rs121913530, rs112445441), and nine (7.50%) in the PIK3CA gene (rs121913273, rs104886003, and rs121913279). No mutations were found in the AKT1, BRAF, and HRAS genes. Six (27.27%) of the 22 genotyping assays called mutations in at least one sample and three (50%) of the six assays queried were found to be mutated more than once. Conclusions: Mutations in the EGFR pathway occurred in a small fraction of Chinese breast cancers. However, therapeutics targeting these potential predictive markers should be investigated in depth, especially in Oriental populations.

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참고문헌

  1. Batzer AG, Rotin D, Urena JM, et al (1994). Hierarchy of binding sites for Grb2 and Shc on the epidermal growth factor receptor. Mol Cell Biol, 14, 5192-201. https://doi.org/10.1128/MCB.14.8.5192
  2. Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, et al (2007). Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res, 67, 2643-8. https://doi.org/10.1158/0008-5472.CAN-06-4158
  3. Chan TO, Rittenhouse SE, Tsichlis PN (1999). AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation. Annu Rev Biochem, 68, 965-1014. https://doi.org/10.1146/annurev.biochem.68.1.965
  4. Cheang MC, Voduc D, Bajdik C, et al (2008). Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res, 14, 1368-76. https://doi.org/10.1158/1078-0432.CCR-07-1658
  5. Davies H, Bignell GR, Cox C et al (2002). Mutations of the BRAF gene in human cancer. Nature, 417, 949-54. https://doi.org/10.1038/nature00766
  6. Dickler MN, Cobleigh MA, Miller KD, et al (2009). Efficacy and safety of erlotinib in patients with locally advanced or metastatic breast cancer. Breast Cancer Res Treat, 115, 115-21. https://doi.org/10.1007/s10549-008-0055-9
  7. Dickler MN, Rugo HS, Eberle CA, et al (2008). A phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer. Clin Cancer Res, 14, 7878-83. https://doi.org/10.1158/1078-0432.CCR-08-0141
  8. Dunlap J, Le C, Shukla, A, et al (2010). Phosphatidylinositol-3-kinase and AKT1 mutations occur early in breast carcinoma. Breast Cancer Res Treat, 120, 409-18. https://doi.org/10.1007/s10549-009-0406-1
  9. Gollamudi R, Ghalib MH, Desai KK, et al. (2010). Intravenous administration of Reolysin, a live replication competent RNA virus is safe in patients with advanced solid tumors. Invest New Drugs, 28, 641-9. https://doi.org/10.1007/s10637-009-9279-8
  10. Green MD, Francis PA, Gebski V, et al (2009). Gefitinib treatment in hormone-resistant and hormone receptornegative advanced breast cancer. Ann Oncol, 20(11), 1813-1817. https://doi.org/10.1093/annonc/mdp202
  11. Gutteridge E, Agrawal A, Nicholson R, et al (2010). The effects of gefitinib in tamoxifen-resistant and hormone-insensitive breast cancer: a phase II study. Int J Cancer, 126(8), 1806-16. https://doi.org/10.1002/ijc.24884
  12. Kadota M, Sato M, Duncan B, et al (2009). Identification of novel gene amplifications in breast cancer and coexistence of gene amplification with an activating mutation of PIK3CA. Cancer Res, 69, 7357-65. https://doi.org/10.1158/0008-5472.CAN-09-0064
  13. Kalinsky K, Jacks LM, Heguy A, et al (2009). PIK3CA mutation associates with improved outcome in breast cancer. Clin Cancer Res, 15, 5049-59. https://doi.org/10.1158/1078-0432.CCR-09-0632
  14. Kan Z, Jaiswal BS, Stinson J, et al. (2010). Diverse somatic mutation patterns and pathway alterations in human cancers. Nature, 466, 869-73. https://doi.org/10.1038/nature09208
  15. Kehr EL, Jorns JM, Ang D, et al (2012). Mucinous breast carcinomas lack PIK3CA and AKT1 mutations. Hum Pathol.
  16. Kononen J, Bubendorf L, Kallioniemi A, et al (1998). Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med, 4, 844-7. https://doi.org/10.1038/nm0798-844
  17. Lee JW, Soung YH, Kim SY, et al (2005). PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. Oncogene, 24, 1477-80. https://doi.org/10.1038/sj.onc.1208304
  18. Leong SP, Shen ZZ, Liu TJ, et al (2010). Is breast cancer the same disease in Asian and Western countries? World J Surg, 34, 2308-24. https://doi.org/10.1007/s00268-010-0683-1
  19. Li SY, Rong M, Grieu F, et al (2006). PIK3CA mutations in breast cancer are associated with poor outcome. Breast Cancer Res Treat, 96, 91-5. https://doi.org/10.1007/s10549-005-9048-0
  20. Liang X, Lau QC, Salto-Tellez M, et al (2006).Mutational hotspot in exon 20 of PIK3CA in breast cancer among Singapore Chinese. Cancer Biol Ther, 5, 544-8. https://doi.org/10.4161/cbt.5.5.2656
  21. Lowenstein EJ, Daly RJ, Batzer AG, et al (1992). The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell, 70, 431-42. https://doi.org/10.1016/0092-8674(92)90167-B
  22. Lv N, Xie X, Ge Q, et al (2011). Epidermal growth factor receptor in breast carcinoma: association between gene copy number and mutations. Diagn Pathol, 6, 118. https://doi.org/10.1186/1746-1596-6-118
  23. MacConaill LE, Campbell CD, Kehoe S M, et al (2009). Profiling critical cancer gene mutations in clinical tumor samples. PLoS One, 4, e7887. https://doi.org/10.1371/journal.pone.0007887
  24. Martin V, Botta F, Zanellato E, et al (2012). Molecular characterization of EGFR and EGFR-downstream pathways in triple negative breast carcinomas with basal like features. Histol Histopathol, 27, 785-92.
  25. Maruyama N, Miyoshi Y, Taguchi T, et al (2007). Clinicopathologic analysis of breast cancers with PIK3CA mutations in Japanese women. Clin Cancer Res, 13, 408-14. https://doi.org/10.1158/1078-0432.CCR-06-0267
  26. Modi S, D'Andrea G, Norton L, et al (2006). A phase I study of cetuximab/paclitaxel in patients with advanced-stage breast cancer. Clin Breast Cancer, 7, 270-7. https://doi.org/10.3816/CBC.2006.n.040
  27. Perez-Tenorio G, Alkhori L, Olsson B, et al (2007). PIK3CA mutations and PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer. Clin Cancer Res, 13, 3577-84. https://doi.org/10.1158/1078-0432.CCR-06-1609
  28. Saal LH, Holm K, Maurer M, et al (2005). PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res, 65, 2554-9. https://doi.org/10.1158/0008-5472-CAN-04-3913
  29. Sholl LM, Xiao Y, Joshi V, et al (2010). EGFR mutation is a better predictor of response to tyrosine kinase inhibitors in non-small cell lung carcinoma than FISH, CISH, and immunohistochemistry. Am J Clin Pathol, 133, 922-34. https://doi.org/10.1309/AJCPST1CTHZS3PSZ
  30. Sinn HP, Helmchen B, et al (2010). [TNM classification of breast cancer: changes and comments on the 7th edition]. Pathologe, 31, 361-6. https://doi.org/10.1007/s00292-010-1307-0
  31. Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, et al (2008). An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res, 68, 6084-91. https://doi.org/10.1158/0008-5472.CAN-07-6854
  32. Troxell ML, Levine J, Beadling C, et al (2010). High prevalence of PIK3CA/AKT pathway mutations in papillary neoplasms of the breast. Mod Pathol, 23, 27-37. https://doi.org/10.1038/modpathol.2009.142
  33. Tsuda H, Morita D, Kimura M, et al. (2005). Correlation of KIT and EGFR overexpression with invasive ductal breast carcinoma of the solid-tubular subtype, nuclear grade 3, and mesenchymal or myoepithelial differentiation. Cancer Sci, 96, 48-53. https://doi.org/10.1111/j.1349-7006.2005.00009.x
  34. Tsutsui S, Kataoka A, Ohno S, et al (2002). Prognostic and predictive value of epidermal growth factor receptor in recurrent breast cancer. Clin Cancer Res, 8, 3454-60.
  35. Uramoto H, Shimokawa H, Nagata Y, et al (2010). EGFRactivating mutations are not present in breast tumors of Japanese patients. Anticancer Res, 30, 4219-22.
  36. Walker RA, Dearing SJ (1999). Expression of epidermal growth factor receptor mRNA and protein in primary breast carcinomas. Breast Cancer Res Treat, 53, 167-76. https://doi.org/10.1023/A:1006194700667
  37. Wang L, Zhang Q, Zhang J, et al (2011). PI3K pathway activation results in low efficacy of both trastuzumab and lapatinib. BMC Cancer, 11, 248. https://doi.org/10.1186/1471-2407-11-248

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