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. 2021 May 24;22(11):5561.
doi: 10.3390/ijms22115561.

High Concordance of Genomic Profiles between Primary and Metastatic Colorectal Cancer

Seung Eun Lee  1 , Ha Young Park  2 , Dae-Yong Hwang  3 , Hye Seung Han  1
Affiliations

High Concordance of Genomic Profiles between Primary and Metastatic Colorectal Cancer

Seung Eun Lee et al. Int J Mol Sci. .

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.

Keywords: genomic profiles; high concordance between primary and metastatic colorectal cancer; metastatic colorectal cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview of mutational profile of 95 pairs of primary-metastatic colorectal cancers. Each column represents a patient. The top 4 panels show MSI status, site of metastasis, patterns of metastasis and number of variant counts per patients. The bottom panel show mutational status, shared, only in primary and only in metastasis. When there are 2 or more mutation type presents, (i.e., ‘shared’ and ‘primary only’) ‘shared’ is preferentially used. The right panel represents the number of patients with variants as bar graph and concordance of the variants as percentage of corresponding genes.
Figure 2
Figure 2
(A) Comparison of mutational frequencies between 95 pairs of primary and metastatic tumors. It is the proportion of patients with mutations in the gene. Top six genes are annotated. (B) Comparison of variant allele frequencies of top six genes between 95 pairs of primary and metastatic tumors. Boxplots show the distribution of VAFs in each group and dots connected by dashed-lines represent same patients. Statistical significance is based on paired two sample t-test and p < 0.05 is marked with asterisk (*).
Figure 3
Figure 3
Landscape of mutations in 99 primary and 142 metastatic groups (including 95 pairs of primary and metastatic tumors). Each column represents a single patient. The percentage of mutations across each group is represented by vertical histograms.
Figure 4
Figure 4
Most commonly mutated gene frequencies of present study compared with TCGA dataset as control for 99 primary group, and MSKCC dataset as control for 142 metastatic group.
See this image and copyright information in PMC

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