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; Joakim Lundeberg

doi:10.1038/s41586-022-05023-2

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. KhavariFiraz Tarish, Anna Tanoglidi, Jonas Maaskola, Richard Colling, Tuomas Mirtti, Freddie C. Hamdy, Dan J. Woodcock, Thomas Helleday, Ian G. Mills, Alastair D. Lamb, Joakim Lundeberg

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137 Scopus citations

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.

Original language	English
Pages (from-to)	360-367
Number of pages	8
Journal	Nature
Volume	608
Issue number	7922
DOIs	https://doi.org/10.1038/s41586-022-05023-2
State	Published - 11 Aug 2022
Externally published	Yes

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Erickson, A., He, M., Berglund, E., Marklund, M., Mirzazadeh, R., Schultz, N., Kvastad, L., Andersson, A., Bergenstråhle, L., Bergenstråhle, J., Larsson, L., Alonso Galicia, L., Shamikh, A., Basmaci, E., Díaz De Ståhl, T., Rajakumar, T., Doultsinos, D., Thrane, K., Ji, A. L., ... Lundeberg, J. (2022). Spatially resolved clonal copy number alterations in benign and malignant tissue. Nature, 608(7922), 360-367. https://doi.org/10.1038/s41586-022-05023-2

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title = "Spatially resolved clonal copy number alterations in benign and malignant tissue",

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.",

author = "Andrew Erickson and Mengxiao He and Emelie Berglund and Maja Marklund and Reza Mirzazadeh and Niklas Schultz and Linda Kvastad and Alma Andersson and Ludvig Bergenstr{\aa}hle and Joseph Bergenstr{\aa}hle and Ludvig Larsson and {Alonso Galicia}, Leire and Alia Shamikh and Elisa Basmaci and {D{\'i}az De St{\aa}hl}, Teresita and Timothy Rajakumar and Dimitrios Doultsinos and Kim Thrane and Ji, {Andrew L.} and Khavari, {Paul A.} and Firaz Tarish and Anna Tanoglidi and Jonas Maaskola and Richard Colling and Tuomas Mirtti and Hamdy, {Freddie C.} and Woodcock, {Dan J.} and Thomas Helleday and Mills, {Ian G.} and Lamb, {Alastair D.} and Joakim Lundeberg",

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year = "2022",

month = aug,

day = "11",

doi = "10.1038/s41586-022-05023-2",

language = "English",

volume = "608",

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journal = "Nature",

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Erickson, A, He, M, Berglund, E, Marklund, M, Mirzazadeh, R, Schultz, N, Kvastad, L, Andersson, A, Bergenstråhle, L, Bergenstråhle, J, Larsson, L, Alonso Galicia, L, Shamikh, A, Basmaci, E, Díaz De Ståhl, T, Rajakumar, T, Doultsinos, D, Thrane, K, Ji, AL, Khavari, PA, Tarish, F, Tanoglidi, A, Maaskola, J, Colling, R, Mirtti, T, Hamdy, FC, Woodcock, DJ, Helleday, T, Mills, IG, Lamb, AD & Lundeberg, J 2022, 'Spatially resolved clonal copy number alterations in benign and malignant tissue', Nature, vol. 608, no. 7922, pp. 360-367. https://doi.org/10.1038/s41586-022-05023-2

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

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 -

Spatially resolved clonal copy number alterations in benign and malignant tissue

Abstract

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