Wise and Lawrence in Nature:
The major cause of cancer-related deaths is the spread of cancer cells from their primary site to other parts of the body1. This spreading process, known as metastasis, typically involves cellular stressors and environmental shocks that induce dramatic changes in cancer cells. One such change is a fierce resistance to current therapies, which means that new ways to combat metastatic disease are urgently needed. Writing in Nature, Priestley et al.2 use whole-genome sequencing (WGS) to illuminate the genomic changes that underpin metastasis in 22 types of solid tumour. Although previous studies3,4 have unearthed some hints of such changes, this is perhaps the first pan-cancer metastasis study of its size to exploit the power of WGS.
Priestley et al. characterized 2,520 samples of metastatic tumours from people with cancer (Fig. 1). In each case, they also analysed a sample of non-cancerous blood cells from the same person. Using WGS, the authors produced a rich catalogue of the genetic mutations found in each metastasis. This catalogue complements existing inventories from both metastasis-sequencing studies and genomic databases of primary tumours, and offers several interesting insights. For example, the authors reveal frequent mutations in the gene MLK4; this is consistent with a previous study that connected an increased number of copies of MLK4 with metastasis5.