Comparison of gene mutations of liver metastases to the primary tumor in colorectal cancer: lessons from a small cohort

Abstract

Introduction Upfront molecular diagnostics are used to characterize genetic features of colorectal cancer, guiding therapy. Since colorectal cancer is usually surgically resected, these samples are used for such characterizations. The extent to which liver metastases maintain the genetic profile of the primary tumor is a key question. Methods Here, we used a small six-case pretreatment colorectal cancer cohort where targeted next-generation sequencing (NGS) was employed to compare liver metastases to the primary tumors. Results We found, similar to previous reports, that the major genetic drivers are maintained in the liver metastases; however, changes at this level can still be detected. We also observed that in the majority of cases, the genetic profile of the primary tumor is partially or completely lost in liver metastases. On the other hand, we detected the metastasis-selective emergence of ABL1, HER2, RET, KIT, KDR, and VHL mutations. Discussion Although our study is only hypothesis-generating, these data support the view that genetic analysis of colorectal cancer liver metastases may identify novel alterations compared to the primary tumors, which can be clinically exploited during disease management.