Clinical Implication of Concordant or Discordant Genomic Profiling between Primary and Matched Metastatic Tissues in Patients with Colorectal Cancer
- Author:
Jung Yoon CHOI
1
;
Sunho CHOI
;
Minhyeok LEE
;
Young Soo PARK
;
Jae Sook SUNG
;
Won Jin CHANG
;
Ju Won KIM
;
Yoon Ji CHOI
;
Jin KIM
;
Dong-Sik KIM
;
Sung-Ho LEE
;
Junhee SEOK
;
Kyong Hwa PARK
;
Seon Hahn KIM
;
Yeul Hong KIM
Author Information
- Publication Type:Original Article
- From:Cancer Research and Treatment 2020;52(3):764-778
- CountryRepublic of Korea
- Language:0
-
Abstract:
Purpose:The purpose of this study was to identify the concordant or discordant genomic profiling between primary and matched metastatic tumors in patients with colorectal cancer (CRC) and to explore the clinical implication.
Materials and Methods:Surgical samples of primary and matched metastatic tissues from 158 patients (335 samples) with CRC at Korea University Anam Hospital were evaluated using the Ion AmpliSeq Cancer Hotspot Panel. We compared genetic variants and classified them as concordant, primary-specific, and metastasis-specific variants. We used a combination of principal components analysis and clustering to find genomic groups. Kaplan-Meier curves were used to appraise survival between genomic groups. We used machine learning to confirm the correlation between genetic variants and metastatic sites.
Results:A total of 282 types of deleterious non-synonymous variants were selected for analysis. Of a total of 897 variants, an average of 40% was discordant. Three genomic groups were yielded based on the genomic discrepancy patterns. Overall survival differed significantly between the genomic groups. The poorest group had the highest proportion of concordant KRAS G12V and additional metastasis-specific SMAD4. Correlation analysis between genetic variants and metastatic sites suggested that concordant KRAS mutations would have more disseminated metastases.
Conclusion:Driver gene mutations were mostly concordant; however, discordant or metastasis-specific mutations were present. Clinically, the concordant driver genetic changes with additional metastasis-specific variants can predict poor prognosis for patients with CRC.
