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Spatially resolved clonal copy number alterations in benign and malignant tissue

Author

Listed:
  • 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
    Karolinska University Hospital)

  • Elisa Basmaci

    (Karolinska Institutet
    Karolinska University Hospital)

  • Teresita Díaz De Ståhl

    (Karolinska Institutet
    Karolinska University Hospital)

  • 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
    Oxford University Hospitals NHS Foundation Trust)

  • Tuomas Mirtti

    (University of Helsinki & Helsinki University Hospital
    University of Helsinki
    iCAN–Digital Precision Cancer Medicine Flagship)

  • Freddie C. Hamdy

    (University of Oxford
    Oxford University Hospitals NHS Foundation Trust)

  • Dan J. Woodcock

    (University of Oxford
    Big Data Institute, University of Oxford)

  • Thomas Helleday

    (Karolinska Institutet
    University of Sheffield)

  • Ian G. Mills

    (University of Oxford)

  • Alastair D. Lamb

    (University of Oxford
    Oxford University Hospitals NHS Foundation Trust)

  • Joakim Lundeberg

    (KTH Royal Institute of Technology, Science for Life Laboratory)

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.

Suggested Citation

  • Andrew Erickson & Mengxiao He & Emelie Berglund & Maja Marklund & Reza Mirzazadeh & Niklas Schultz & Linda Kvastad & Alma Andersson & Ludvig Bergenstråhle & Joseph Bergenstråhle & Ludvig Larsson & Lei, 2022. "Spatially resolved clonal copy number alterations in benign and malignant tissue," Nature, Nature, vol. 608(7922), pages 360-367, August.
    • Handle: RePEc:nat:nature:v:608:y:2022:i:7922:d:10.1038_s41586-022-05023-2
    DOI: 10.1038/s41586-022-05023-2
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    Citations

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    Cited by:

    1. Shadi Shafighi & Agnieszka Geras & Barbara Jurzysta & Alireza Sahaf Naeini & Igor Filipiuk & Alicja Ra̧czkowska & Hosein Toosi & Łukasz Koperski & Kim Thrane & Camilla Engblom & Jeff E. Mold & Xinsong, 2024. "Integrative spatial and genomic analysis of tumor heterogeneity with Tumoroscope," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Elena Denisenko & Leanne Kock & Adeline Tan & Aaron B. Beasley & Maria Beilin & Matthew E. Jones & Rui Hou & Dáithí Ó Muirí & Sanela Bilic & G. Raj K. A. Mohan & Stuart Salfinger & Simon Fox & Khaing , 2024. "Spatial transcriptomics reveals discrete tumour microenvironments and autocrine loops within ovarian cancer subclones," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Zhenzhen Xun & Xinyu Ding & Yao Zhang & Benyan Zhang & Shujing Lai & Duowu Zou & Junke Zheng & Guoqiang Chen & Bing Su & Leng Han & Youqiong Ye, 2023. "Reconstruction of the tumor spatial microenvironment along the malignant-boundary-nonmalignant axis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Rohit Arora & Christian Cao & Mehul Kumar & Sarthak Sinha & Ayan Chanda & Reid McNeil & Divya Samuel & Rahul K. Arora & T. Wayne Matthews & Shamir Chandarana & Robert Hart & Joseph C. Dort & Jeff Bier, 2023. "Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    5. Zhixing Zhong & Junchen Hou & Zhixian Yao & Lei Dong & Feng Liu & Junqiu Yue & Tiantian Wu & Junhua Zheng & Gaoliang Ouyang & Chaoyong Yang & Jia Song, 2024. "Domain generalization enables general cancer cell annotation in single-cell and spatial transcriptomics," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    6. Nikita Sushentsev & Gregory Hamm & Lucy Flint & Daniel Birtles & Aleksandr Zakirov & Jack Richings & Stephanie Ling & Jennifer Y. Tan & Mary A. McLean & Vinay Ayyappan & Ines Horvat Menih & Cara Brodi, 2024. "Metabolic imaging across scales reveals distinct prostate cancer phenotypes," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    7. Ning Zhang & Luuk Harbers & Michele Simonetti & Constantin Diekmann & Quentin Verron & Enrico Berrino & Sara E. Bellomo & Gabriel M. C. Longo & Michael Ratz & Niklas Schultz & Firas Tarish & Peng Su &, 2024. "High clonal diversity and spatial genetic admixture in early prostate cancer and surrounding normal tissue," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    8. Rongting Huang & Xianjie Huang & Yin Tong & Helen Y. N. Yan & Suet Yi Leung & Oliver Stegle & Yuanhua Huang, 2024. "Robust analysis of allele-specific copy number alterations from scRNA-seq data with XClone," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    9. Hao Xu & Shuyan Wang & Minghao Fang & Songwen Luo & Chunpeng Chen & Siyuan Wan & Rirui Wang & Meifang Tang & Tian Xue & Bin Li & Jun Lin & Kun Qu, 2023. "SPACEL: deep learning-based characterization of spatial transcriptome architectures," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    10. Maja Marklund & Niklas Schultz & Stefanie Friedrich & Emelie Berglund & Firas Tarish & Anna Tanoglidi & Yao Liu & Ludvig Bergenstråhle & Andrew Erickson & Thomas Helleday & Alastair D. Lamb & Erik Son, 2022. "Spatio-temporal analysis of prostate tumors in situ suggests pre-existence of treatment-resistant clones," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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