Spatial atlas of clonal copy number alterations in co-existing benign and malignant tissue

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

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 2 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001008644	Spatial transcriptome sequence data from two tumour containing prostates. Entire cross section of organ divided into cubes to fit spatial transcriptomics arrays. The dataset contains paired-end sequences from 21 sections of 1k array sections and 9 sections of 10x Visium sections for patient 1 as well as 28 sections of 10x Visium sections for patient 2.	Illumina NovaSeq 6000 unspecified	58

Publications	Citations
Spatially resolved clonal copy number alterations in benign and malignant tissue. 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. Nature 608: 2022 360-367	45
Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures. Figiel S, Yin W, Doultsinos D, Erickson A, Poulose N, Singh R, Magnussen A, Anbarasan T, Teague R, He M, Lundeberg J, Loda M, Verrill C, Colling R, Gill PS, Bryant RJ, Hamdy FC, Woodcock DJ, Mills IG, Cussenot O, Lamb AD. Mol Cancer 22: 2023 162	1

Publications

Citations

Spatially resolved clonal copy number alterations in benign and malignant tissue.
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. Nature 608: 2022 360-367

Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures.
Figiel S, Yin W, Doultsinos D, Erickson A, Poulose N, Singh R, Magnussen A, Anbarasan T, Teague R, He M, Lundeberg J, Loda M, Verrill C, Colling R, Gill PS, Bryant RJ, Hamdy FC, Woodcock DJ, Mills IG, Cussenot O, Lamb AD. Mol Cancer 22: 2023 162