TY - JOUR
T1 - Spatially resolved clonal copy number alterations in benign and malignant tissue
AU - Erickson, Andrew
AU - He, Mengxiao
AU - Berglund, Emelie
AU - Marklund, Maja
AU - Mirzazadeh, Reza
AU - Schultz, Niklas
AU - Kvastad, Linda
AU - Andersson, Alma
AU - Bergenstråhle, Ludvig
AU - Bergenstråhle, Joseph
AU - Larsson, Ludvig
AU - Alonso Galicia, Leire
AU - Shamikh, Alia
AU - Basmaci, Elisa
AU - Díaz De Ståhl, Teresita
AU - Rajakumar, Timothy
AU - Doultsinos, Dimitrios
AU - Thrane, Kim
AU - Ji, Andrew L.
AU - Khavari, Paul A.
AU - Tarish, Firaz
AU - Tanoglidi, Anna
AU - Maaskola, Jonas
AU - Colling, Richard
AU - Mirtti, Tuomas
AU - Hamdy, Freddie C.
AU - Woodcock, Dan J.
AU - Helleday, Thomas
AU - Mills, Ian G.
AU - Lamb, Alastair D.
AU - Lundeberg, Joakim
N1 - Funding Information:
This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 101021019). The study was also supported by the Swedish Cancer Society, Swedish Foundation for Strategic Research, AstraZeneca and Science for Life Laboratory. We also acknowledge the Swedish Childhood Tumour Biobank, supported by the Swedish Childhood Cancer Fund, for access and handling of patient biobank material/sequencing data and the Swedish Childhood Cancer Fund. We would like to thank the National Genomics Infrastructure, Sweden, for providing infrastructure support. We thank A. Mollbrink, X.M. Abalo, M. Nistér and P. Lundin for helpful assistance and discussions. A.D.L. was supported by a Cancer Research UK Clinician Scientist Fellowship award (C57899/A25812) that also funded A.E. F.C., R.C. and A.D.L. have received support from the Oxford National Institute for Health Research (NIHR) Biomedical Research Centre Surgical Innovation and Evaluation Theme. I.G.M. is grateful to the John Black Charitable Foundation for support, and D.J.W. is grateful to the Cancer Research UK Oxford Centre. Computation used the Oxford Biomedical Research Computing facility, a joint development between the Wellcome Centre for Human Genetics and the Big Data Institute supported by Health Data Research UK and the NIHR Oxford Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. We appreciate the kind assistance of A. Ståhl, R.A. Novoa and K. Rieger with additional histology assessment of specimens in this study. We appreciate the kind assistance of S. Tuomisto and W. Yin for their technical assistance and feedback on code development. We also thank S. Figiel for assistance with spatial transcriptomics technical developments and feedback on data analysis and visualization.
Funding Information:
This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 101021019). The study was also supported by the Swedish Cancer Society, Swedish Foundation for Strategic Research, AstraZeneca and Science for Life Laboratory. We also acknowledge the Swedish Childhood Tumour Biobank, supported by the Swedish Childhood Cancer Fund, for access and handling of patient biobank material/sequencing data and the Swedish Childhood Cancer Fund. We would like to thank the National Genomics Infrastructure, Sweden, for providing infrastructure support. We thank A. Mollbrink, X.M. Abalo, M. Nistér and P. Lundin for helpful assistance and discussions. A.D.L. was supported by a Cancer Research UK Clinician Scientist Fellowship award (C57899/A25812) that also funded A.E. F.C., R.C. and A.D.L. have received support from the Oxford National Institute for Health Research (NIHR) Biomedical Research Centre Surgical Innovation and Evaluation Theme. I.G.M. is grateful to the John Black Charitable Foundation for support, and D.J.W. is grateful to the Cancer Research UK Oxford Centre. Computation used the Oxford Biomedical Research Computing facility, a joint development between the Wellcome Centre for Human Genetics and the Big Data Institute supported by Health Data Research UK and the NIHR Oxford Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. We appreciate the kind assistance of A. Ståhl, R.A. Novoa and K. Rieger with additional histology assessment of specimens in this study. We appreciate the kind assistance of S. Tuomisto and W. Yin for their technical assistance and feedback on code development. We also thank S. Figiel for assistance with spatial transcriptomics technical developments and feedback on data analysis and visualization.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/8/11
Y1 - 2022/8/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85135833407&partnerID=8YFLogxK
U2 - 10.1038/s41586-022-05023-2
DO - 10.1038/s41586-022-05023-2
M3 - Article
C2 - 35948708
AN - SCOPUS:85135833407
SN - 0028-0836
VL - 608
SP - 360
EP - 367
JO - Nature
JF - Nature
IS - 7922
ER -