Neutral tumor evolution?

Abstract

To the Editor — Tumor growth is an evolutionary process that is governed by somatic mutation, clonal selection and random genetic drift, and is constrained by the coevolution of the microenvironment1,2. Tumor subclones are subpopulations of tumor cells with a common set of mutations resulting from the expansion of a single cell during tumor development, and they have been observed in a substantial fraction of cancers and across multiple cancer types3. Peter Nowell has proposed that tumors evolve through sequential genetic events4, whereby one cell acquires a selective advantage so that its lineage becomes predominant. According to this traditional model, the selective advantage is conferred by a small set of driver mutations, but as the subclones that bear them successively expand, they also accumulate passenger mutations, which can be detected in sequencing experiments1. Genomes of individual tumors contain hundreds to many thousands of these genetic variants at a wide range of frequencies5,6. Because genetic drift can drive novel variants to high frequencies, it is of great interest to discern the relative importance of selection and drift in shaping the frequency distribution of variants in any given tumor.