# Clonal dispersal is associated with tumor heterogeneity and poor prognosis in colorectal cancer

## TL;DR

This paper shows that clonal dispersal in colorectal cancer is linked to tumor diversity and worse patient outcomes, offering a new way to predict prognosis.

## Contribution

The study introduces a fluorescent cell barcoding method to quantify clonal dispersal and identifies a dispersal gene signature as a prognostic marker.

## Key findings

- Clonal dispersal is correlated with epithelial-mesenchymal transition and CMS4 signaling pathways.
- A dispersal gene signature is a robust predictor of poor prognosis and recurrence in CRC.
- Clonal dispersal varies across CRC models and is associated with intratumor heterogeneity.

## Abstract

Clonal dispersal, resulting from the intermingling of tumor cell subpopulations, is thought to be a key driver of tumor heterogeneity. Despite advances in spatial modeling of cancer biology, quantification of clonal dispersal has been challenging. This study introduces a straightforward method, relying on fluorescent cell barcoding, to quantify clonal dispersal in various in vitro and in vivo models of colorectal cancer (CRC). Our approach allows for precise localization of clones and uncovering the degree of clonal mixing across different CRC models. Our findings suggest that clonal dispersal is correlated with the expression of genes involved in epithelial-mesenchymal transition and CMS4-related signaling pathways. We further identify a dispersal gene signature, associated with intratumor heterogeneity, which is a robust clinical predictor of poor prognosis and recurrence in CRC, highlighting its potential as a prognostic marker and a putative direction for therapeutic targeting.

•Clonal dispersal is quantifiable and cell line specific•Dispersal is associated with EMT and the mesenchymal CMS4 CRC subtype•Dispersal correlates with intratumor heterogeneity and poor clinical outcome

Clonal dispersal is quantifiable and cell line specific

Dispersal is associated with EMT and the mesenchymal CMS4 CRC subtype

Dispersal correlates with intratumor heterogeneity and poor clinical outcome

Cell biology; Bioinformatics; Cancer