A new branch on the tree: next-generation sequencing in the study of cancer evolution

Abstract

Cancer is a disease caused by the accumulation of genetic alterations in association with successive waves of clonal expansion. Mapping of the human genome sequence, in conjunction with technical advances in the ability to sequence entire genomes, have provided new insight into the mutational spectra and genetic events associated with clonal evolution of cancer. Moving forward, a clearer understanding of those alterations that undergo positive and negative selection throughout carcinogenesis and leading to metastatic dissemination would provide a boon not only to our understanding of cancer evolution, but to the development of potential targets for therapeutic intervention as well.

Figure 1. Schematic of intratumoral clonal evolution

Neoplasia begins when a genetic alteration (denoted by M) occurs in a normal cell that confers a selective growth advantage. Over time, additional alterations accumulate in the progeny of this cell, leading to successive waves of clonal expansion and the eventual formation of subclones with differing abilities to metastasize and evade treatment. Subclonal evolution is believed to follow Darwinian selection in that some subclones will become extinguished by others with greater abilities to survive in the tenuous microenvironment of the neoplasm.