Quantifying disease burden in patients with cancer using tumour-specific genomic rearrangements (360G-Wellcome-092002_Z_10_Z)

Cancer is caused by the accumulation of genetic damage (mutations) in cells within a particular organ. These mutations are only found in the cancerous cells and therefore could be used to track the malignancy during treatment. Advances in DNA sequencing allow the high-throughput identification of these mutations from any cancer sample in a clinically relevant time-frame. As tumour cells die, they release their DNA into the bloodstream. Dr Peter Campbell, Wellcome Trust Sanger Institute and colleagues propose to use the new generation of genetic sequencing technologies to identify a particular class of mutations caused by the abnormal rearrangement of chromosomes in patients with breast cancer and colorectal cancer.From these rearrangements, the team will develop assays to detect DNA from each patient's cancer that has been released into the bloodstream. Such assays will be highly specific (minimal risk of falsely positive results) and sensitive (capable of detecting one copy of tumour DNA in many millilitres of blood). The programme will measure the amount of disease using blood samples collected before surgery, after surgery, during chemotherapy and at regular time-points post-therapy. Dr Campbell and colleagues will therefore be able to assess the ability of this approach to identify high-risk patients before treatment begins, to monitor response to treatment and to predict cancer relapse before it is clinically apparent.