Genome-wide 3D-transcriptomics reveals localized immune system activity and subtype-heterogeneity in HER2+ breast tumors
Fredrik Salmén1†, Sanja Vickovic1†, Linnea Stenbeck1, Johan Vallon-Christersson2, Anna Ehinger2, 3, Jari Häkkinen2, Åke Borg2, Jonas Frisén4, Patrik L Ståhl1, 4*, Joakim Lundeberg1
1Science for Life Laboratory, Division of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden; 2Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden; 3Department of Pathology and Cytology, Blekinge County Hospital, Karlskrona, Sweden; 4Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
Comprehensive analysis of tumor tissue is crucial for determining specific disease states and establishing suitable treatment plans. Here, we analyze tumor tissue from patients with HER2+ breast cancer to obtain genome-wide three-dimensional expression data. We track regional heterogeneity of ductal cancer in situ with its adjacent regions to reveal a mutually exclusive immune system response in the three-dimensional tumor microenvironment. We also detect and visualize intrinsic molecular subtypes using the AIMS classification system showing that HER2+ breast tumors can contain several distinct subtypes within the same invasive region. The increased granularity provided by detailed spatial transcriptomes throughout a tumor can be used to decipher a number of biological questions, and in turn have a direct impact on the clinical decision-making process.