Mutational analysis of key EGFR pathway genes in Chinese breast cancer patients

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Abstract

Background: The epidermal growth factor receptor (EGFR) is a potential therapeutic target forbreast 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 mutationswere detected in 12 (10%) of the samples, all of which were invasive ductal carcinomas (two stageI, 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 indepth, especially in Oriental populations.

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Tong, L., Yang, X. X., Liu, M. F., Yao, G. Y., Dong, J. Y., Ye, C. S., & Li, M. (2012). Mutational analysis of key EGFR pathway genes in Chinese breast cancer patients. Asian Pacific Journal of Cancer Prevention, 13(11), 5599–5603. https://doi.org/10.7314/APJCP.2012.13.11.5599

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