Intratumor genetic heterogeneity dictates metastatic subclones in stage II colon cancer

Authors

• M Sahu
• R Lafyatis
• P Gourh

Abstract

Although standard therapies are highly effective in stage II colon cancers (CC), some patients show disease relapse within the next 5-year period after intended curative surgery. We hypothesize that genomic instability and intratumor heterogeneity fuel the formation of subclonal populations in the primary tumor that might promote metastasis.

Our study assesses the presence of intratumor heterogeneity in CC using multiplex interphase FISH and whole-exome sequencing in nine primary stage II colon tumors and their patient-matched liver metastases using multi-region sampling.
We observed high similarities regarding copy-number alterations (CNA) and ploidy between primary tumor and metastasis for three of four cases analyzed. Two of these cases showed either triploid or highly aneuploid genomes with different degrees of genomic instability. Both matched lesions for the third case displayed diploid clones, however, the primary tumor revealed two distinct cell populations with either CDX2 diploid or gained. The metastasis seems to originate from the CDX2 diploid clone. Conversely, the fourth case revealed a triploid baseline for the primary tumor while diploid for the metastasis. Although five of the CNA observed in the tumor and metastasis major clone populations were similar, two highly clonal gains observed in the tumor, EGFR and MYC, were not present in the metastasis.
In summary, we show that the combined analysis of WES and miFISH can describe the subclonal composition of CNA in primary tumors and their liver metastases.
Future perspectives include the assessment of subclonality affecting single-nucleotide variants to complete the genomic landscape of tumor evolution and clonal development.

Scientific Focus Area: Cancer Biology

This page was last updated on Monday, September 25, 2023