High Concordance of Genomic Profiles between Primary and Metastatic Colorectal Cancer.

Seung Eun Lee,Ha Young Park,Dae-Yong Hwang,Hye Seung Han

doi:10.3390/ijms22115561

Abstract

The comparison of the genetic profiles between primary and metastatic colorectal cancer (CRC) is needed to enable the discovery of useful therapeutic targets against metastatic CRCs. We performed the targeted next generation sequencing assay of 170 cancer-associated genes for 142 metastatic CRCs, including 95 pairs of primary and metastatic CRCs, to reveal their genomic characteristics and to assess the genetic heterogeneity. The most frequently mutated gene in primary and metastatic CRCs was APC (71% vs. 65%), TP53 (54% vs. 57%), KRAS (45% vs. 44%), PIK3CA (16% vs. 19%), SMAD4 (15% vs. 14%) and FBXW7 (11% vs. 11%). The concordance in the top six frequently mutated genes was 85%, on average. The overall mutation frequencies were consistent with two sets of public data (TCGA and MSKCC). To the author’s knowledge, this is the first study to compare the genetic profiles of our cohort with that of the metastatic CRCs from MSKCC. Comparative sequencing analysis between primary and metastatic CRCs revealed a high degree of genetic concordance in the current clinically actionable genes. Therefore, the genetic investigation of archived primary tumor samples with the challenges of obtaining an adequate sample from metastatic sites appears to be sufficient for the application of cancer precision medicine in the metastatic setting.

Highlights

IntroductionColorectal cancer (CRC) is one of the well-established tumor types to be considered as a genetic disease in which the multiple and sequential accumulation of genetic alterations underlies the development and progression to carcinoma and metastasis
We identified that the frequency of recurrent mutations of APC, KRAS, PIK3CA, FBXW7, and SMAD4 were consistent with previous reports on metastatic Colorectal cancer (CRC) [3,12,13]
Additional metastatic only samples were included for mutational profiling of metastatic tumors and primary only samples were used as a control for metastatic tumors

Summary

Introduction

Colorectal cancer (CRC) is one of the well-established tumor types to be considered as a genetic disease in which the multiple and sequential accumulation of genetic alterations underlies the development and progression to carcinoma and metastasis. Several studies have performed the analysis of the comparative genetic sequencing of paired primary and metastatic CRC [4,5,6,7]. The majority have shown a high degree of concordance in the genetic profile between primary and metastatic CRC [4,5,6]. Early recurrent genetic alterations such as APC, KRAS, NRAS, and BRAF, involving colorectal carcinogenesis, were highly concordant in matched pairs of primary and metastatic CRC [5,6]

Methods

Results

Discussion

Conclusion