Jakubek, Y. A. et al. Nat. Biotechnol. https://doi.org/10.1038/s41587-019-0297-6 (2019).

Many cancer cells harbor high levels of genomic variation. While some of these somatic mutations are likely to drive oncogenesis, a comprehensive picture of their origin, prevalence and role in tumor and non-tumor cells is still under investigation. Jakubek et al. analyzed SNP array genotype data from 1,708 normal-appearing adjacent-to-tumor (NAT) tissue samples (27 cancer sites) and 7,149 blood samples from The Cancer Genome Atlas (TCGA) dataset. By focusing on megabase-scale somatic copy number alterations (sCNAs), they identified widespread sCNAs in different NAT and blood samples. More sCNAs were detected in NAT samples than in blood samples, and there is heterogeneity in rate and genomic distribution among cancer sites. Although some NAT tissues share sCNAs with adjacent tumor, others independently accumulate their own set of sCNAs, even targeting the same oncogenes. This framework and analysis deepen our understanding of genomic variation in tissues appearing normal upon pathology examination and their role in tumor origin.