High clonal diversity and spatial genetic admixture in early prostate cancer and surrounding normal tissue

Sep 21, 2026

High clonal diversity and spatial genetic admixture are investigated in early, localized prostate cancer and adjacent normal tissue. Using multi-region, single-cell DNA sequencing in two prostatectomy patients, the study maps somatic copy number alterations (SCNAs) across tumor-rich and normal regions. Two karyotype classes are defined: pseudodiploid cells with few SCNAs and aneuploid cells with extensive alterations. Pseudodiploid cells form many small subclones, from highly localized to broadly spread, while aneuploid cells appear throughout the prostate, including normal areas.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Introduction

SCNA prevalence and early formation

Spatial heterogeneity in localized prostate cancer

Prior spatial transcriptomics evidence

Methods and Approach

Multi-region single-cell copy number profiling

Targeted deep sequencing of matched regions

Results

SCNA landscape across tumor-rich and normal tissues

Two karyotype classes: pseudodiploid vs aneuploid

Subclonal spatial patterns in localized disease

Implications

Article [https://doi.org/10.1038/s41467-024-47664-z](https://doi.org/10.1038/s41467-024-47664-z) High clonal diversity and spatial genetic admixture in early prostate cancer and surrounding normal tissue Received: 10 August 2023 | Accepted: 9 April 2024 | | --- | | | | Check for updates | Ning Zhang1,2,14,15, Luuk Harbers 1,2,15, Michele Simonetti 1,2,15, Constantin Diekmann 1,2, Quentin Verron1,2, Enrico Berrino 3,4, Sara E. Bellomo3,5, Gabriel M. C. Longo 6, Michael Ratz 7, Niklas Schultz2,8, Firas Tarish9, Peng Su10, Bo Han10, Wanzhong Wang8, Soﬁa Onorato1,2, Dora Grassini4, Roberto Ballarino 1,2, Silvia Giordano 3,5, Qifeng Yang11, Anna Sapino 3,4, Jonas Frisén 7, Kanar Alkass7,8, Henrik Druid 8, Vassilis Roukos 6,12, Thomas Helleday 2,8, Caterina Marchiò3,4, Magda Bienko 1,2,13 & Nicola Crosetto 1,2,13 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: ‘pseudodiploid’ 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 tumorrich 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. Somatic copy number alterations (SCNAs) are pervasive in human cancers1–3. It has been proposed that SCNAs form in the early stages of tumorigenesis in punctuated evolutionary bursts4–7. Indeed, SCNAs have been detected in pre-malignant lesions such as Barret’s esophagus years before the onset of invasive esophageal cancer8 and oral leukoplakias undergoing progressive transformation to oralsquamous cell carcinomas9. However, the exact timing and mechanisms of SCNA formation during carcinogenesis remain poorly 1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 17177, Sweden. 2Science for Life Laboratory, Stockholm 17177, Sweden. 3Candiolo Cancer Institute, FPO – IRCCS, Candiolo, SP142, km 3,95, 10060 Turin, Italy. 4Department of Medical Sciences, University of Turin, Turin, Italy. 5Department of Oncology, University of Turin, Turin, Italy. 6Institute of Molecular Biology(IMB), Mainz55128, Germany. 7Department of Celland Molecular Biology, Karolinska Institute, Stockholm 17177, Sweden. 8Department of Oncology and Pathology, Karolinska Institutet, Stockholm 17177, Sweden. 9Södersjukhuset, Stockholm 11883, Sweden. 10Department of Pathology, Qilu Hospital of Shandong University, Ji’nan 250012, China. 11Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Ji’nan 250012, China. 12Department of General Biology, Medical School, University of Patras, Patras, Greece. 13Human Technopole, Viale Rita Levi-Montalcini 1, 20157 Milan, Italy. 14Present address: Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Ji’nan 250012, China. 15These authors contributed equally: Ning Zhang, Luuk Harbers, Michele Simonetti. e-mail: nicola.crosetto@ki.se understood and a map of SCNAs in early-stage, localized tumors and their surrounding normal tissues is missing. In prostate cancers, SCNAs represent the predominant type of genomic alteration and are thought to be the major driver of these tumors10. Early-stage localized prostat

FAQs

What technique is used to characterize SCNAs across prostate regions?

The study performs multi-region, single-cell DNA sequencing to profile somatic copy number alterations across tumor-rich and surrounding normal tissue.

How many karyotype classes are identified in early localized tumors?

Two distinct karyotypes are identified: pseudodiploid cells with few SCNAs and highly aneuploid cells with extensive alterations.

How do pseudodiploid and aneuploid cells differ in spatial distribution?

Pseudodiploid cells form numerous small subclones with spatial patterns ranging from highly localized to broadly spread, while aneuploid cells are detected throughout the prostate, including normal regions.

Sep 21, 2026

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