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David Wedge

David Wedge

David Wedge

BA PGCE MSc PhD


Group Leader in Cancer Genomics, Nuffield Department of Medicine

The focus of my research is cancer evolution and heterogeneity. Cancers are made up of a heterogeneous mix of cells, each bearing a different set of mutations in its DNA. We aim to characterise groups of cells, or ‘subclones’, according to their mutational profiles and to study the interaction between subclones.

Tumours are difficult to treat because they change over time, gaining mutations that enable them to metastasise to distant organs or that result in resistance to treatment. By comparing multiple samples, we can identify those mutations that cause relapse and progression. Using genetic markers, we can also track the spread of disease, giving us insights into the mechanisms and processes involved in cancer growth and metastasis.

International Cancer Genome Consortium

Cancer is a complex disease and the analysis of large numbers of tumours is key to understanding the factors that determine their virulence. The International Cancer Genome Consortium (ICGC) has collected and Whole-Genome Sequenced several thousand cancer samples. I co-lead the Pan-Cancer Analysis of Whole Genomes (PCAWG) Working Group on Evolution and Heterogeneity, an international collaboration that is using the DNA sequences of 2800 of these cancer samples to study evolution and heterogeneity across more than 30 different cancer types, including prostate, breast, lung, oesophageal and ovarian cancers.

The 100,000 Genomes project has whole-genome sequenced 25,000 cancers through Genomics England. Through the NIHR Oxford Biomedical Centre (BRC) Molecular Diagnostics theme, members of my research group are analysing the DNA sequences of colorectal, endometrial and testicular cancers from the 100,000 Genomes project, with the aim of extending the scope of precision medicine. Through the BRC, we are also using novel sequencing technologies to gain further insights into tumour heterogeneity.

Through the Pan Prostate Cancer Group (PPCG), we are analysing Whole Genome Sequences of over 1200 prostate cancers. The main aims of this project are to: identify multimodal biomarkers of aggressive disease; provide new insights into prostate cancer diagnosis and mechanisms of development; identify new insights into ethnic differences in the propensity to develop aggressive prostate cancer; identify new markers of genetic predisposition to prostate cancer.

Software

We have developed software packages for the purpose of studying tumour evolution and heterogeneity, including:

  • The Battenberg algorithm, which identifies clonal and subclonal copy number aberrations. The Battenberg package may be downloaded from here.
  • Octopus, a mapping-based variant caller that calls single nucleotide variants (SNVs) and small insertions and deletions (indels) using a haplotype-aware framework. Octopus may be downloaded from here.

Key publications

Recent publications

More publications