Evolutionary analysis of origin of cancer metastases

Evolutionary analysis of origin of cancer metastases

Many aspects of tumor formation remain poorly understood, including the origins of metastatic lineages.

To study how metastases arise, researchers used evolutionary biology tools to analyze exome sequences from 32 primary tumors and 139 metastatic sites from 40 volunteers.

The authors’ analysis supported a nonlinear model of cancer progression, in which metastatic tumors originate from divergent lineages within primary tumors rather than descending from a single departing primary tumor cell.

The authors examined the timing of gene mutations and how the mutations contributed to tumor formation. The results suggest that a specific series of genetic changes are unlikely to be required to give rise to metastases, with heritable genetic and epigenetic events that occur early in tumor evolution likely only affecting the tendency toward metastasis.

In addition, the authors found that metastatic lineages are produced stochastically and arise early in tumor development, sometimes well before diagnosis of the primary tumor. The study’s analyses could help elucidate the timing of mutations in driver genes that occur early in cancer evolution.

According to the authors, these mutations could serve as therapeutic targets against both primary tumors and metastases.