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Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer

Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of subclonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones, even years after removal of the prostate. Analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of subclones with metastatic potential which we can detect in the blood.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001001343 Illumina HiSeq 2000 15
EGAD00001001344 Illumina HiSeq 2000 6
EGAD00001001345 Illumina HiSeq 2000 12
Publications Citations
Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer.
Nat Commun 6: 2015 6605
198
Minimal functional driver gene heterogeneity among untreated metastases.
Science 361: 2018 1033-1037
147
Inferring structural variant cancer cell fraction.
Nat Commun 11: 2020 730
24
Spatially resolved clonal copy number alterations in benign and malignant tissue.
Nature 608: 2022 360-367
56