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

Study ID	Alternative Stable ID	Type
EGAS00001000942		Other

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.

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. 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. 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. 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

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

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

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

Study

Study Description

Study Datasets 3 datasets.

Who archives the data?

Publications

Citations

The European Genome-phenome Archive (EGA) is part of the ELIXIR infrastructure.