Spatially resolved clonal copy number alterations in benign and malignant tissue

Andrew Erickson, Mengxiao He, Emelie Berglund, Maja Marklund, Reza Mirzazadeh, Niklas Schultz, Linda Kvastad, Alma Andersson, Ludvig Bergenstråhle, Joseph Bergenstråhle, Ludvig Larsson, Leire Alonso Galicia, Alia Shamikh, Elisa Basmaci, Teresita Díaz De Ståhl, Timothy Rajakumar, Dimitrios Doultsinos, Kim Thrane, Andrew L. Ji, Paul A. Khavari, Firaz Tarish, Anna Tanoglidi, Jonas Maaskola, Richard Colling, Tuomas Mirtti, Freddie C. Hamdy, Dan J. Woodcock, Thomas Helleday, Ian G. Mills, Alastair D. Lamb () and Joakim Lundeberg ()
Additional contact information
Andrew Erickson: University of Oxford
Mengxiao He: KTH Royal Institute of Technology, Science for Life Laboratory
Emelie Berglund: KTH Royal Institute of Technology, Science for Life Laboratory
Maja Marklund: KTH Royal Institute of Technology, Science for Life Laboratory
Reza Mirzazadeh: KTH Royal Institute of Technology, Science for Life Laboratory
Niklas Schultz: Karolinska Institutet
Linda Kvastad: KTH Royal Institute of Technology, Science for Life Laboratory
Alma Andersson: KTH Royal Institute of Technology, Science for Life Laboratory
Ludvig Bergenstråhle: KTH Royal Institute of Technology, Science for Life Laboratory
Joseph Bergenstråhle: KTH Royal Institute of Technology, Science for Life Laboratory
Ludvig Larsson: KTH Royal Institute of Technology, Science for Life Laboratory
Leire Alonso Galicia: KTH Royal Institute of Technology, Science for Life Laboratory
Alia Shamikh: Karolinska Institutet
Elisa Basmaci: Karolinska Institutet
Teresita Díaz De Ståhl: Karolinska Institutet
Timothy Rajakumar: University of Oxford
Dimitrios Doultsinos: University of Oxford
Kim Thrane: KTH Royal Institute of Technology, Science for Life Laboratory
Andrew L. Ji: Stanford University School of Medicine
Paul A. Khavari: Stanford University School of Medicine
Firaz Tarish: Karolinska Institutet
Anna Tanoglidi: University Uppsala Hospital
Jonas Maaskola: KTH Royal Institute of Technology, Science for Life Laboratory
Richard Colling: University of Oxford
Tuomas Mirtti: University of Helsinki & Helsinki University Hospital
Freddie C. Hamdy: University of Oxford
Dan J. Woodcock: University of Oxford
Thomas Helleday: Karolinska Institutet
Ian G. Mills: University of Oxford
Alastair D. Lamb: University of Oxford
Joakim Lundeberg: KTH Royal Institute of Technology, Science for Life Laboratory

Nature, 2022, vol. 608, issue 7922, 360-367

Abstract: Abstract Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer1. Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics2 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 using an organ-wide approach focused on the prostate. 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 capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.

Date: 2022
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Citations: View citations in EconPapers (11)

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DOI: 10.1038/s41586-022-05023-2

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