Somatic copy number alterations (SCNAs) are pervasive in advanced human cancers, but their prevalence and spatial distribution in early-stage, localized tumors and their surrounding normal tissues are poorly characterized. Here, we perform multi-region, single-cell DNA sequencing to characterize the SCNA landscape across tumor-rich and normal tissue in two male patients with localized prostate cancer. We identify two distinct karyotypes: 'pseudo-diploid' cells harboring few SCNAs and highly aneuploid cells. Pseudo-diploid cells form numerous small-sized subclones ranging from highly spatially localized to broadly spread subclones. In contrast, aneuploid cells do not form subclones and are detected throughout the prostate, including normal tissue regions. Highly localized pseudo-diploid subclones are confined within tumor-rich regions and carry deletions in multiple tumor-suppressor genes. Our study reveals that SCNAs are widespread in normal and tumor regions across the prostate in localized prostate cancer patients and suggests that a subset of pseudo-diploid cells drive tumorigenesis in the aging prostate.
Nature communications. 2024 Apr 24*** epublish ***
Ning Zhang, Luuk Harbers, Michele Simonetti, Constantin Diekmann, Quentin Verron, Enrico Berrino, Sara E Bellomo, Gabriel M C Longo, Michael Ratz, Niklas Schultz, Firas Tarish, Peng Su, Bo Han, Wanzhong Wang, Sofia Onorato, Dora Grassini, Roberto Ballarino, Silvia Giordano, Qifeng Yang, Anna Sapino, Jonas Frisén, Kanar Alkass, Henrik Druid, Vassilis Roukos, Thomas Helleday, Caterina Marchiò, Magda Bienko, Nicola Crosetto
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, 17177, Sweden., Candiolo Cancer Institute, FPO - IRCCS, Candiolo, SP142, km 3,95, 10060, Turin, Italy., Institute of Molecular Biology (IMB), Mainz, 55128, Germany., Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, 17177, Sweden., Science for Life Laboratory, Stockholm, 17177, Sweden., Södersjukhuset, Stockholm, 11883, Sweden., Department of Pathology, Qilu Hospital of Shandong University, Ji'nan, 250012, China., Department of Oncology and Pathology, Karolinska Institutet, Stockholm, 17177, Sweden., Department of Medical Sciences, University of Turin, Turin, Italy., Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Ji'nan, 250012, China., Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, 17177, Sweden. .