The evolutionary history of lethal metastatic prostate cancer

ICGC Prostate UK Group, G. Steven Bova

Research output: Contribution to journalArticle

Abstract

Cancers emerge from an ongoing Darwinian evolutionary process, often leading to multiple competing subclones within a single primary tumour. This evolutionary process culminates in the formation of metastases, which is the cause of 90% of cancer-related deaths. However, despite its clinical importance, little is known about the principles governing the dissemination of cancer cells to distant organs. Although the hypothesis that each metastasis originates from a single tumour cell is generally supported, recent studies using mouse models of cancer demonstrated the existence of polyclonal seeding from and interclonal cooperation between multiple subclones. Here we sought definitive evidence for the existence of polyclonal seeding in human malignancy and to establish the clonal relationship among different metastases in the context of androgen-deprived metastatic prostate cancer. Using whole-genome sequencing, we characterized multiple metastases arising from prostate tumours in ten patients. Integrated analyses of subclonal architecture revealed the patterns of metastatic spread in unprecedented detail. Metastasis-to-metastasis spread was found to be common, either through de novo monoclonal seeding of daughter metastases or, in five cases, through the transfer of multiple tumour clones between metastatic sites. Lesions affecting tumour suppressor genes usually occur as single events, whereas mutations in genes involved in androgen receptor signalling commonly involve multiple, convergent events in different metastases. Our results elucidate in detail the complex patterns of metastatic spread and further our understanding of the development of resistance to androgen-deprivation therapy in prostate cancer.

Original languageEnglish (US)
Pages (from-to)353-357
Number of pages5
JournalNature
Volume520
Issue number7547
DOIs
StatePublished - Apr 15 2015

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Prostatic Neoplasms
History
Neoplasm Metastasis
Neoplasms
Androgens
Androgen Receptors
Tumor Suppressor Genes
Prostate
Clone Cells
Genome
Mutation
Genes

ASJC Scopus subject areas

  • General

Cite this

ICGC Prostate UK Group, & Bova, G. S. (2015). The evolutionary history of lethal metastatic prostate cancer. Nature, 520(7547), 353-357. https://doi.org/10.1038/nature14347

The evolutionary history of lethal metastatic prostate cancer. / ICGC Prostate UK Group; Bova, G. Steven.

In: Nature, Vol. 520, No. 7547, 15.04.2015, p. 353-357.

Research output: Contribution to journalArticle

ICGC Prostate UK Group & Bova, GS 2015, 'The evolutionary history of lethal metastatic prostate cancer', Nature, vol. 520, no. 7547, pp. 353-357. https://doi.org/10.1038/nature14347
ICGC Prostate UK Group, Bova GS. The evolutionary history of lethal metastatic prostate cancer. Nature. 2015 Apr 15;520(7547):353-357. https://doi.org/10.1038/nature14347
ICGC Prostate UK Group ; Bova, G. Steven. / The evolutionary history of lethal metastatic prostate cancer. In: Nature. 2015 ; Vol. 520, No. 7547. pp. 353-357.
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