The spatial landscape of clonal expansion by confined somatic mutations in benign and malignant tissue
Session type: E-poster/poster
Defining the transition from benign tissue to tumor is fundamental to improve 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 (Visium, 10x Genomics) to infer spatial copy number variations in >120 000 spatial regions across multiple organs, tissues and tumors, including three prostates, two childhood brain cancers, skin cancer, breast cancer and a lymph node.
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 histo-pathologically benign tissue that may represent early events in cancer evolution. We perform an in-depth spatial analysis of prostate cancer that includes an unprecedented interrogation of up to 50 000 tissue domains in a single patient, and 120 000 tissue domains across 10 patients. For these domains we inferred genome-wide information in each spot, which facilitated data driven clustering in a tissue wide fashion at high resolution. Furthermore the spatial information allowed us to identify small clonal units not evident from morphology and hence would be overlooked by histologically-guided laser microdissection or even random sampling of single cells.
In this analysis of a total of 9 patients, 3 whole prostates, 6 different tissue types, 66 sections, over 120,000 spatial regions, we present the first large-scale, comprehensive atlas of genomic evolution at high spatial resolution within cancer.
We highlight the power of an unsupervised approach to capture the molecular and spatial continuums in a tissue context and challenge the rationale for focal treatment in a number of cancers, particularly prostate cancer - we also expect our approach to be of interest to researchers investigating the biological basis of somatic mosaicism and tissue development.