Rapid evolution and biogeographic spread in a colorectal cancer

Joao M Alves,José Manuel Cameselle-Teijeiro,David Posada,Sonia Prado-López

doi:10.1038/s41467-019-12926-8

Abstract

How and when tumoral clones start spreading to surrounding and distant tissues is currently unclear. Here we leveraged a model-based evolutionary framework to investigate the demographic and biogeographic history of a colorectal cancer. Our analyses strongly support an early monoclonal metastatic colonization, followed by a rapid population expansion at both primary and secondary sites. Moreover, we infer a hematogenous metastatic spread under positive selection, plus the return of some tumoral cells from the liver back to the colon lymph nodes. This study illustrates how sophisticated techniques typical of organismal evolution can provide a detailed, quantitative picture of the complex tumoral dynamics over time and space.

Highlights

How and when tumoral clones start spreading to surrounding and distant tissues is currently unclear
In metastatic colorectal cancer many aspects underlying the dissemination of cancer cells to tissues beyond primary lesions have been difficult to determine
A principal component analysis (PCA) of their allele frequencies showed a clear distinction between primary tumor and metastatic samples (Fig. 1b)

Summary

Introduction

How and when tumoral clones start spreading to surrounding and distant tissues is currently unclear. With the increasing availability of high-throughput genomic data, several studies have started to explore the evolutionary relationships of tumor clones in order to identify the key molecular changes driving cancer progression[2], to better understand the subclonal architecture of tumors[3,4], and to determine the origins of metastases[5]. Earlier models of mCRC progression have proposed a sequential metastatic cascade, with cells from the primary tumor first escaping to local lymph nodes from where they seed distant tissues[10], conflicting evidence has recently emerged, as some genomic datasets seem to favor an independent origin of distant and lymph node metastases[5]. Our results provide an unusually detailed picture of the complex evolution of tumor cell populations within a single individual, identifying tumor demographics and colonization patterns within a defined timeframe

Methods

Results

Conclusion