Genome-wide 3D-transcriptomics reveals localized immune system activity and subtype-heterogeneity in HER2+ breast tumors


Identification: Vickovic, Sanja


Description

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

†Equal contribution

*Corresponding author

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.

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