Shuang-Mei Zou1, Wei-Hua Li1, Wen-Miao Wang1, Wen-Bin Li1, Su-Sheng Shi1, Jian-Ming Ying2, Ning Lyu3. 1. Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People's Republic of China. 2. Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People's Republic of China. jmying@hotmail.com. 3. Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People's Republic of China. nlu03@126.com.
Abstract
PURPOSE: To better understand the gene mutational status and heterogeneity between primary and metastatic CRC (mCRC) using a sensitive sequencing method. METHODS: The mutational status of EGFR, KRAS, NRAS, PIK3CA, ERBB2, BRAF, KIT, and PDGFRA was analyzed in 65 patients, with 147 samples of primary and paired live or lung metastatic CRC, using next-generation sequencing (NGS), quantitative RT-PCR (qPCR), and Sanger sequencing. RESULTS: Fifteen cases (15/22, 68.2%) of lung mCRC and thirteen cases (13/20, 65%) of liver mCRC harboured the same mutation profiles of KRAS, NRAS, or BRAF in the primary lesions. To all detected genes, 11 cases (11/22, 50%) of lung mCRC and 11 cases (11/20, 55%) of liver mCRC showed different mutational genes in the primary tumours. KRAS and BRAF mutations were more frequent in lung metastatic lesions (p = 0.004 and 0.003, respectively). The gene mutations in KRAS, NRAS, BRAF, and PIK3CA in the lung metastatic sites were more frequent than those in the liver metastatic sites (86.7 vs. 44%, respectively, p = 0.000). Some new mutations were not covered in the qPCR ranges but were detected by NGS. CONCLUSION: The study demonstrated that the discordance of gene mutational status between paired primary and metastatic tumours is rather high when detected by NGS. Evaluating the mutational status of both the primary and metastatic tumours should be considered in clinical mutation testing.
PURPOSE: To better understand the gene mutational status and heterogeneity between primary and metastatic CRC (mCRC) using a sensitive sequencing method. METHODS: The mutational status of EGFR, KRAS, NRAS, PIK3CA, ERBB2, BRAF, KIT, and PDGFRA was analyzed in 65 patients, with 147 samples of primary and paired live or lung metastatic CRC, using next-generation sequencing (NGS), quantitative RT-PCR (qPCR), and Sanger sequencing. RESULTS: Fifteen cases (15/22, 68.2%) of lung mCRC and thirteen cases (13/20, 65%) of liver mCRC harboured the same mutation profiles of KRAS, NRAS, or BRAF in the primary lesions. To all detected genes, 11 cases (11/22, 50%) of lung mCRC and 11 cases (11/20, 55%) of liver mCRC showed different mutational genes in the primary tumours. KRAS and BRAF mutations were more frequent in lung metastatic lesions (p = 0.004 and 0.003, respectively). The gene mutations in KRAS, NRAS, BRAF, and PIK3CA in the lung metastatic sites were more frequent than those in the liver metastatic sites (86.7 vs. 44%, respectively, p = 0.000). Some new mutations were not covered in the qPCR ranges but were detected by NGS. CONCLUSION: The study demonstrated that the discordance of gene mutational status between paired primary and metastatic tumours is rather high when detected by NGS. Evaluating the mutational status of both the primary and metastatic tumours should be considered in clinical mutation testing.
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