TY - JOUR T1 - The spatial landscape of clonal somatic mutations in benign and malignant tissue JF - bioRxiv DO - 10.1101/2021.07.12.452018 SP - 2021.07.12.452018 AU - Andrew Erickson AU - Emelie Berglund AU - Mengxiao He AU - Maja Marklund AU - Reza Mirzazadeh AU - Niklas Schultz AU - Ludvig Bergenstråhle AU - Linda Kvastad AU - Alma Andersson AU - Joseph Bergenstråhle AU - Ludvig Larsson AU - Alia Shamikh AU - Elisa Basmaci AU - Teresita Diaz De Ståhl AU - Timothy Rajakumar AU - Kim Thrane AU - Andrew L Ji AU - Paul A Khavari AU - Firaz Tarish AU - Anna Tanoglidi AU - Jonas Maaskola AU - Richard Colling AU - Tuomas Mirtti AU - Freddie C Hamdy AU - Dan J Woodcock AU - Thomas Helleday AU - Ian G. Mills AU - Alastair D Lamb AU - Joakim Lundeberg Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/07/12/2021.07.12.452018.abstract N2 - Defining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. Here, we provide an unsupervised approach to study spatial genome integrity in situ to gain molecular insight into clonal relationships. We employed spatially resolved transcriptomics to infer spatial copy number variations in >120 000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of an unsupervised approach to capture the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.Competing Interest StatementJL, MH, MJ, RM, LK, AA, LL and JL are scientific consultants to 10x Genomics Inc. ER -