Decoding Cancer Evolution Through Genomic Analysis of Tumour Clonal Dynamics
This review describes how somatic mutations accumulated during tumour growth serve as a molecular record of cancer evolution, enabling retrospective reconstruction of clonal dynamics from a single biopsy. The authors argue that distinguishing neutral drift from positive selection is essential for interpreting tumour heterogeneity and that punctuated phenotype evolution can arise from both gradual and sudden genomic changes. Understanding the genotype-to-phenotype relationship is critical for predicting evolutionary trajectories and informing therapeutic strategies.
The original study
Measuring cancer evolution from the genome.
- Authors
- Graham TA, Sottoriva A
- Journal
- The Journal of pathology
- Type
- Journal Article, Review
- PMID
- 27741350
Original abstract
The temporal dynamics of cancer evolution remain elusive, because it is impractical to longitudinally observe cancers unperturbed by treatment. Consequently, our knowledge of how cancers grow largely derives from inferences made from a single point in time - the endpoint in the cancer's evolution, when it is removed from the body and studied in the laboratory. Fortuitously however, the cancer genome, by virtue of ongoing mutations that uniquely mark clonal lineages within the tumour, provides a rich, yet surreptitious, record of cancer development. In this review, we describe how a cancer's genome can be analysed to reveal the temporal history of mutation and selection, and discuss why both selective and neutral evolution feature prominently in carcinogenesis. We argue that selection in cancer can only be properly studied once we have some understanding of what the absence of selection looks like. We review the data describing punctuated evolution in cancer, and reason that punctuated phenotype evolution is consistent with both gradual and punctuated genome evolution. We conclude that, to map and predict evolutionary trajectories during carcinogenesis, it is critical to better understand the relationship between genotype change and phenotype change. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.