# Whole-genome sequencing of 2,520 metastatic tumours from the Dutch Hartwig cohort

Source: https://onco.cc/key-papers/paper-priestley-hartwig-metastatic-wgs-nature-2019/  
OnCo record `paper-priestley-hartwig-metastatic-wgs-nature-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The Hartwig Medical Foundation's whole-genome analysis of metastatic cancers from Dutch patients found a variant that could steer treatment towards an approved or trial drug in 62 per cent of them.

## Summary

The abstract describes what it calls the largest pan-cancer study of metastatic solid tumour genomes to that date: whole-genome sequencing of 2,520 pairs of tumour and normal tissue, at median depths of 106 and 38 times, surveying more than 70 million somatic variants. The mutations of metastatic lesions varied widely and largely reflected the primary tumour types, with whole-genome duplication in 56 per cent. Individual lesions were relatively homogeneous: 96 per cent of driver mutations were clonal and up to 80 per cent of tumour-suppressor genes were inactivated on both alleles. For 62 per cent of patients the authors identified variants that could be used to direct them towards therapies that were approved or in clinical trials.

## Fields

- Kind: Key paper
- Last checked: 2026-11-03
- Journal: Nature
- Year: 2019
- DOI: 10.1038/s41586-019-1689-y
- Authors: Priestley P, Baber J, Lolkema MP, et al.
- Findings: Whole-genome sequencing of 2,520 metastatic tumour and normal pairs, at median depths of 106x and 38x.; Whole-genome duplication in 56% of metastatic tumours.; 96% of driver mutations were clonal.; 62% of patients had a variant that could direct them to an approved or trial therapy.
- What it means: This is the cohort behind the Hartwig Medical Database, which the foundation describes as the largest of its kind, offered free of charge to researchers. It showed whole-genome sequencing of metastases done at national scale, and found a variant that could point to a treatment in most of the patients sequenced.
- Caveats: Actionable is not the same as benefited: the paper counts variants that could direct treatment, not outcomes after treatment.; Patients were those referred into Dutch trial and sequencing programmes, not a population sample.

## Sources

- Nature 2019: https://doi.org/10.1038/s41586-019-1689-y
- PubMed: https://pubmed.ncbi.nlm.nih.gov/31645765/
- Hartwig Medical Database: https://www.hartwigmedicalfoundation.nl/en/data/database/

## Connected records

- trials: [DRUP (Drug Rediscovery Protocol)](https://onco.cc/trials/drup/)
- technologies: [Whole-exome & whole-genome sequencing](https://onco.cc/technologies/wes-wgs/)
- companies: [Hartwig Medical Foundation](https://onco.cc/companies/hartwig-medical-foundation/)
- key papers: [The Drug Rediscovery Protocol: approved cancer drugs used outside their licence, inside a national trial](https://onco.cc/key-papers/paper-drup-van-der-velden-nature-2019/)

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