Stem-Like Adaptive Aneuploidy and Cancer Quasispecies

TL;DR

This paper proposes that tumor cells can self-regulate their aneuploidy rate through mechanisms similar to stem cells, and uses a quasispecies model to analyze how genomic instability affects tumor fitness.

Contribution

It introduces a novel model applying quasispecies theory to cancer, linking aneuploidy regulation to stem cell mechanisms and estimating an error threshold for tumor viability.

Findings

Tumor cells may self-regulate their aneuploidy rate.

A quasispecies model can predict the error threshold for tumor fitness.

Highly aneuploid tumors operate near the estimated error threshold.

Abstract

We analyze and reinterpret experimental evidence from the literature to argue for an ability of tumor cells to self-regulate their aneuploidy rate. We conjecture that this ability is mediated by a diversification factor that exploits molecular mechanisms common to embryo stem cells and, to a lesser extent, adult stem cells, that is eventually reactivated in tumor cells. Moreover, we propose a direct use of the quasispecies model to cancer cells based on their significant genomic instability (i.e. aneuploidy rate), by defining master sequences lengths as the sum of all copy numbers of physically distinct whole and fragmented chromosomes. We compute an approximate error threshold such that any aneuploidy rate larger than the threshold would lead to a loss of fitness of a tumor population, and we confirm that highly aneuploid cancer populations already function with aneuploidy rates close to the estimated threshold.