학술논문
Spatially resolved clonal copy number alterations in benign and malignant tissue
Document Type
Article
Author
Erickson, Andrew; He, Mengxiao; Berglund, Emelie; Marklund, Maja; Mirzazadeh, Reza; Schultz, Niklas; Kvastad, Linda; Andersson, Alma; Bergenstråhle, Ludvig; Bergenstråhle, Joseph; Larsson, Ludvig; Alonso Galicia, Leire; Shamikh, Alia; Basmaci, Elisa; Díaz De Ståhl, Teresita; Rajakumar, Timothy; Doultsinos, Dimitrios; Thrane, Kim; Ji, Andrew L.; Khavari, Paul A.; Tarish, Firaz; Tanoglidi, Anna; Maaskola, Jonas; Colling, Richard; Mirtti, Tuomas; Hamdy, Freddie C.; Woodcock, Dan J.; Helleday, Thomas; Mills, Ian G.; Lamb, Alastair D.; Lundeberg, Joakim
Source
Nature; August 2022, Vol. 608 Issue: 7922 p360-367, 8p
Subject
Language
ISSN
00280836; 14764687
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 transcriptomics2to 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.