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Multi-cancer analysis of clonality and the timing of systemic spread in paired primary tumors and metastases.

ABSTRACT: Metastasis is the primary cause of cancer-related deaths, but the natural history, clonal evolution and impact of treatment are poorly understood. We analyzed whole-exome sequencing (WES) data from 457 paired primary tumor and metastatic samples from 136 patients with breast, colorectal and lung cancer, including untreated (n?=?99) and treated (n?=?100) metastases. Treated metastases often harbored private 'driver' mutations, whereas untreated metastases did not, suggesting that treatment promotes clonal evolution. Polyclonal seeding was common in untreated lymph node metastases (n?=?17 out of 29, 59%) and distant metastases (n?=?20 out of 70, 29%), but less frequent in treated distant metastases (n?=?9 out of 94, 10%). The low number of metastasis-private clonal mutations is consistent with early metastatic seeding, which we estimated occurred 2-4 years before diagnosis across these cancers. Furthermore, these data suggest that the natural course of metastasis is selectively relaxed relative to early tumorigenesis and that metastasis-private mutations are not drivers of cancer spread but instead associated with drug resistance.

SUBMITTER: Hu Z

PROVIDER: S-EPMC7343625 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Multi-cancer analysis of clonality and the timing of systemic spread in paired primary tumors and metastases.

Hu Zheng Z Li Zan Z Ma Zhicheng Z Curtis Christina C

Nature genetics 20200518 7

Metastasis is the primary cause of cancer-related deaths, but the natural history, clonal evolution and impact of treatment are poorly understood. We analyzed whole-exome sequencing (WES) data from 457 paired primary tumor and metastatic samples from 136 patients with breast, colorectal and lung cancer, including untreated (n = 99) and treated (n = 100) metastases. Treated metastases often harbored private 'driver' mutations, whereas untreated metastases did not, suggesting that treatment promot ...[more]

PMID: 32424352

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Multi-cancer analysis of clonality and the timing of systemic spread in paired primary tumors and metastases.

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Multi-cancer analysis of clonality and the timing of systemic spread in paired primary tumors and metastases.

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