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

Abstract

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.

Metadata

Item Type:	Article
Authors/Creators:	Zhang, N. Harbers, L. https://orcid.org/0000-0003-3910-6497 Simonetti, M. https://orcid.org/0000-0003-3322-1697 Diekmann, C. https://orcid.org/0000-0002-4779-3541 Verron, Q. Berrino, E. https://orcid.org/0000-0001-6728-5619 Bellomo, S.E. Longo, G.M.C. https://orcid.org/0000-0003-2028-1068 Ratz, M. https://orcid.org/0000-0002-9795-8033 Schultz, N. Tarish, F. Su, P. Han, B. Wang, W. Onorato, S. Grassini, D. Ballarino, R. https://orcid.org/0000-0001-7812-0940 Giordano, S. https://orcid.org/0000-0003-1854-1086 Yang, Q. Sapino, A. https://orcid.org/0000-0003-3542-9571 Frisén, J. https://orcid.org/0000-0001-5819-458X Alkass, K. Druid, H. https://orcid.org/0000-0002-9198-023X Roukos, V. https://orcid.org/0000-0002-5065-3937 Helleday, T. https://orcid.org/0000-0002-7384-092X Marchiò, C. Bienko, M. https://orcid.org/0000-0002-6499-9082 Crosetto, N. https://orcid.org/0000-0002-3019-6978
Copyright, Publisher and Additional Information:	© The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Keywords:	Humans; Male; Prostatic Neoplasms; DNA Copy Number Variations; Single-Cell Analysis; Aneuploidy; Prostate; Clone Cells; Diploidy; Aged
Dates:	Published: 24 April 2024 Published (online): 24 April 2024 Accepted: 9 April 2024
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield)
Depositing User:	Symplectic Sheffield
Date Deposited:	11 Jun 2024 15:36
Last Modified:	11 Jun 2024 15:36
Published Version:	http://dx.doi.org/10.1038/s41467-024-47664-z
Status:	Published
Publisher:	Springer Science and Business Media LLC
Refereed:	Yes
Identification Number:	10.1038/s41467-024-47664-z
Related URLs:	PubMed URL Dataset
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:213302