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Dis Colon Rectum. 2019 Mar 15. doi: 10.1097/DCR.0000000000001386. [Epub ahead of print]

Necessity of Genetic Evaluation of Metachronous Metastases of Colorectal Cancer: Quantitative Analysis of Genetic Discordance Between Metachronous Metastases and Radically Resected Primary Colorectal Cancers Using Next-Generation Sequencing.

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Department of Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea.



Mutation analyses provide the basis of selecting an appropriate target agent for the treatment of metastatic colorectal cancer. However, metachronous metastases developed after the treatment of primary tumor could create significant opportunities for different genetic profiles relative to the primary tumors.


The purpose of this study was to assess the necessity of genetic evaluation of metachronous metastases; we performed a quantitative analysis of genetic discordance between metachronous metastases and radically resected primary colorectal cancers using next-generation sequencing.


This was a retrospective study.


Patients from a single-institution tertiary care center were studied.


We enrolled 33 patients who underwent resection of metachronous metastases between January 2014 and December 2016, ≥6 months after radical resection of primary colorectal cancer and whose tissue was available for analysis.


Tumor samples were analyzed by next-generation sequencing. The mutant allele frequency was analyzed to evaluate the proportion of mutations in the tumor tissue.


The mutant allele frequency of KRAS in metachronous metastases was higher in 6 cases (mean difference =% 25.5% (range, 9.5%-58.0%)) and lower in 3 cases (mean difference = 9.3% (range, 8.0-10.0%) compared with each of their primary tumors. In 1 case, the KRAS mutant-type (mutant allele frequency = 22.6%) metachronous metastasis had developed from the KRAS wild-type primary tumor.


Tumor sample may not represent perfectly the whole tumor of the patient because of heterogeneity.


Genetic discordance can exist between metachronous metastases and radically resected primary colorectal cancers. For appropriate target therapy, genetic evaluation of metachronous metastases needs to be considered when possible. See Video Abstract at

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