Spatially resolved clonal copy number alterations in benign and malignant tissue

被引：126

作者：

Erickson, Andrew ^{[1
]}

He, Mengxiao ^{[2
]}

Berglund, Emelie ^{[2
]}

Marklund, Maja ^{[2
]}

Mirzazadeh, Reza ^{[2
]}

Schultz, Niklas ^{[3
]}

Kvastad, Linda ^{[2
]}

Andersson, Alma ^{[2
]}

Bergenstrahle, Ludvig ^{[2
]}

Bergenstrahle, Joseph ^{[2
]}

Larsson, Ludvig ^{[2
]}

Galicia, Leire Alonso ^{[2
]}

Shamikh, Alia ^{[4
,5
]}

Basmaci, Elisa ^{[4
,5
]}

De Stahl, Teresita Diaz ^{[4
,5
]}

Rajakumar, Timothy ^{[1
]}

Doultsinos, Dimitrios ^{[1
]}

Thrane, Kim ^{[2
]}

Ji, Andrew L. ^{[6
]}

Khavari, Paul A. ^{[6
]}

Tarish, Firaz ^{[3
]}

Tanoglidi, Anna ^{[7
]}

Maaskola, Jonas ^{[2
]}

Colling, Richard ^{[1
,8
]}

Mirtti, Tuomas ^{[9
,10
,11
,12
]}

Hamdy, Freddie C. ^{[1
,13
]}

Woodcock, Dan J. ^{[1
,14
]}

Helleday, Thomas ^{[3
,15
]}

Mills, Ian G. ^{[1
]}

Lamb, Alastair D. ^{[1
,13
]}

Lundeberg, Joakim ^{[2
]}

机构：

[1] Univ Oxford, Nuffield Dept SurgicalSci, Oxford, England

[2] KTH Royal Inst Technol, Dept Gene Technol, Sci Life Lab, Solna, Sweden

[3] Karolinska Inst, Dept Oncol Pathol, Sci Life Lab, Solna, Sweden

[4] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden

[5] Karolinska Univ Hosp, Dept Clin Pathol & Cytol, Stockholm, Sweden

[6] Stanford Univ, Program Epithelial Biol, Sch Med, Stanford, CA USA

[7] Univ Uppsala Hosp, Dept Clin Pathol, Uppsala, Sweden

[8] Oxford Univ Hosp NHS Fdn Trust, Dept Cellular Pathol, Oxford, England

[9] Univ Helsinki, Dept Pathol, Helsinki, Finland

[10] Helsinki Univ Hosp, Helsinki, Finland

[11] Univ Helsinki, Fac Med, Res Program Syst Oncol, Helsinki, Finland

[12] iCAN Digital Precis Canc Med Flagship, Helsinki, Finland

[13] Oxford Univ Hosp NHS Fdn Trust, Dept Urol, Oxford, England

[14] Univ Oxford, Big Data Inst, Oxford, England

[15] Univ Sheffield, Dept Oncol & Metab, Weston Pk Canc Ctr, Sheffield, S Yorkshire, England

来源：

NATURE | 2022年 / 608卷 / 7922期

基金：

欧洲研究理事会;

关键词：

PROSTATE-CANCER; MUTATIONS; GENE;

D O I：

10.1038/s41586-022-05023-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer(1). Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics(2) 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.

引用

页码：360 / +

页数：31

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