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Mutation status of somatic EGFR and KRAS genes in Chinese patients with prostate cancer (PCa)

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Abstract

Activating mutations of the epidermal growth factor receptor (EGFR) confers sensitivity to tyrosine kinase inhibitors (TKIs). In colorectal cancer and in lung adenocarcinomas, clinical trials have shown a lack of response to anti-EGFR therapy when KRAS gene mutations are present. In this study, the mutation status of specified exons of the EGFR and KRAS genes was profiled in patients with prostate cancer (PCa). Direct Sanger sequencing was used to screen for mutations in exons 19–21 of EGFR and in exon 2 of KRAS in 88 Chinese patients diagnosed with prostate adenocarcinomas. Mutations were detected in 11 patients. In nine cases (10 %), activating mutations in the region of EGFR encoding the tyrosine kinase (TK) domain were present. Deletions in exon 19 and the L858R substitution in exon 21 were “hotspot” mutations, together accounting for five (55 %) of nine cases. Many synonymous substitutions were also detected. KRAS mutations were found in two cases (2.3 % of 88). There were no cases with mutations in both EGFR and KRAS, suggesting that mutations in the two genes might be mutually exclusive. Although prognostic relevance of EGFR expression by immunohistochemistry (IHC) was observed in PCa patients in previous studies, we found no statistically significant association between EGFR or KRAS mutations and clinicopathological features (including age, smoking status, preoperative prostate-specific antigen, Gleason scores, and tumor stage). We contend that accurate profiling of the mutation status of EGFR and KRAS could improve prognostic stratification, and we suggest a potential anti-EGFR therapy for patients with PCa with EGFR mutations.

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Acknowledgments

We thank the Chinese Academy of Medical Sciences for support with informatics infrastructure and the Beijing Hospital for providing histology and tissue management support. We are grateful to Jianming Ying and Ling Shan for technical assistance.

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The authors declare that they have no conflict of interest. All authors have read and approved the final version of the manuscript.

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Correspondence to Jimao Zhao.

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Fu, M., Zhang, W., Shan, L. et al. Mutation status of somatic EGFR and KRAS genes in Chinese patients with prostate cancer (PCa). Virchows Arch 464, 575–581 (2014). https://doi.org/10.1007/s00428-014-1566-x

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  • DOI: https://doi.org/10.1007/s00428-014-1566-x

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