Concordance of Acquired Mutations between Metastatic Lesions and Liquid Biopsy in Metastatic Colorectal Cancer Treated with Anti-EGFR Therapy

Abstract Background: Acquired mutations are detected in circulating cell-free DNA or circulating tumor cells in blood. However, there are still few reports that examine the concordance between liquid biopsy and metastatic lesions with acquired resistance. Methods: We examined the presence of acquired mutations in 7 chemoresistant metastatic lesions and blood samples obtained from a metastatic colorectal cancer (mCRC) patient without RAS activating mutations treated with anti-EGFR treatment. The patient displayed initial early tumor shrinkage and finally progressed to disease (PD). The 7 metastatic lesions showing acquired resistance to chemotherapy were extracted at morbid autopsy. Blood samples were collected before the development of PD during first-line chemotherapy and after acquiring resistance to second- and third-line chemotherapies. Acquired mutations were analyzed using two methodologies: conventional Sanger sequencing and MEBGENTM RASKET KIT based on Luminex® technology.Results: Metastatic tumor specimens harbored diverse acquired mutations in the KRAS gene in all of the 7 (100%) metastases in the patient resistant to EGFR-targeted treatment. Of the 7 diverse acquired mutations, only one acquired mutation observed in a liver metastasis was clearly detected in the blood collected at third-line chemotherapies. Two other acquired mutations were also detected but did not reach meaningful values. Conclusions: Liquid biopsy is a successful procedure for capturing acquired mutations that may arise from progressive metastatic lesions with acquired resistance over time.