Study

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

Study ID Alternative Stable ID Type
EGAS00001000942 Other

Study Description

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.

Study Datasets 3 datasets.

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Dataset ID Description Technology Samples
EGAD00001001343
Data from the study of subclonal metastatic expansion in prostate cancer. Whole genome shotgun sequencing of fifteen samples, tumour and whole blood, from the four initial patients.
Illumina HiSeq 2000 15
EGAD00001001344
Data from the study of subclonal metastatic expansion in prostate cancer. Whole genome shotgun sequencing of six samples, tumour and whole blood, from the three additional patients whose somatic variants were examined in depth.
Illumina HiSeq 2000 6
EGAD00001001345
Data from the study of subclonal metastatic expansion in prostate cancer. RNA-seq of twelve samples, tumour and benign tissue, from the four initial patients.
Illumina HiSeq 2000 12

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