The spatial landscape of clonal somatic mutations in benign and malignant tissue

You have accessJournal of UrologyCME1 May 2022MP45-14 THE SPATIAL LANDSCAPE OF CLONAL SOMATIC MUTATIONS IN BENIGN AND MALIGNANT PROSTATE EPITHELIA Andrew Erickson, Emelie Berglund, Mengxiao He, Maja Marklund, Reza Mirzazadeh, Niklas Schultz, Ludvig Bergenstråhle, Linda Kvastad, Alma Andersson, Joseph Bergenstråhle, Ludvig Larsson, Alia Shamikh, Elisa Basmaci, Teresita Diaz De Ståhl, Timothy Rajakumar, Kim Thrane, Andrew Ji, Paul Khavari, Firaz Tarish, Anna Tanoglidi, Jonas Maaskola, Richard Colling, Tuomas Mirtti, Freddie C. Hamdy, Dan Woodcock, Thomas Helleday, Ian Mills, Alastair Lamb, and Joakim Lundeberg Andrew EricksonAndrew Erickson More articles by this author , Emelie BerglundEmelie Berglund More articles by this author , Mengxiao HeMengxiao He More articles by this author , Maja MarklundMaja Marklund More articles by this author , Reza MirzazadehReza Mirzazadeh More articles by this author , Niklas SchultzNiklas Schultz More articles by this author , Ludvig BergenstråhleLudvig Bergenstråhle More articles by this author , Linda KvastadLinda Kvastad More articles by this author , Alma AnderssonAlma Andersson More articles by this author , Joseph BergenstråhleJoseph Bergenstråhle More articles by this author , Ludvig LarssonLudvig Larsson More articles by this author , Alia ShamikhAlia Shamikh More articles by this author , Elisa BasmaciElisa Basmaci More articles by this author , Teresita Diaz De StåhlTeresita Diaz De Ståhl More articles by this author , Timothy RajakumarTimothy Rajakumar More articles by this author , Kim ThraneKim Thrane More articles by this author , Andrew JiAndrew Ji More articles by this author , Paul KhavariPaul Khavari More articles by this author , Firaz TarishFiraz Tarish More articles by this author , Anna TanoglidiAnna Tanoglidi More articles by this author , Jonas MaaskolaJonas Maaskola More articles by this author , Richard CollingRichard Colling More articles by this author , Tuomas MirttiTuomas Mirtti More articles by this author , Freddie C. HamdyFreddie C. Hamdy More articles by this author , Dan WoodcockDan Woodcock More articles by this author , Thomas HelledayThomas Helleday More articles by this author , Ian MillsIan Mills More articles by this author , Alastair LambAlastair Lamb More articles by this author , and Joakim LundebergJoakim Lundeberg More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002611.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Defining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. We aimed to conduct an unsupervised approach to study spatial genome integrity, in situ, to gain molecular insight into clonal relationships. METHODS: We employed spatially resolved transcriptomics (Visium, 10x Genomics) to infer spatial copy number variations in >120 000 spatial regions across multiple organs, tissues and tumors, including three whole axial prostates from patients with primary prostate cancer. We used this information to deduce clonal relationships between regions harboring 5-20 cells. RESULTS: We performed an in-depth spatial analysis of prostate cancer that includes an unprecedented interrogation of up to 50,000 tissue domains in a single patient, and 120,000 tissue domains across 10 patients. For these domains we inferred genome-wide information, which facilitated data driven clustering in a tissue wide fashion at high resolution. We demonstrated that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue. In section H2_1 (Figure 1), we observed that many CNVs occurred in clone C, most notably in chromosome 8. This clone constituted a region of exclusively benign acinar cells branching off a duct lined by largely copy neutral cells in clone A and B. Cancer clones E, F and G then arose from this clone with further mutational events. CONCLUSIONS: In this analysis, we present the first large-scale, comprehensive atlas of genomic evolution at high spatial resolution in prostate cancer. Our results suggest a model for how genomic instability arises in histo-pathologically benign tissue that may represent early events in cancer evolution. Furthermore the spatial information allowed us to identify small clonal units not evident from morphology and which might therefore be overlooked by pathologists. We highlight the power of an unsupervised approach to capture the molecular and spatial continuums in a tissue context and challenge the rationale for focal therapy in prostate cancer. Source of Funding: The Swedish Research Council, The Swedish Cancer Society, The Swedish Childhood Cancer Fund, Swedish Foundation for Strategic Research, Knut and Alice Wallenberg Foundation, Science for Life Laboratory/ Postdoc program, European Research Council Advanced Grant, Cancer Research UK Clinician Scientist Fellowship, John Black Charitable Foundation, Cancer Foundation Finland, Hospital District of Helsinki and Uusimaa, Academy of Finland, NIHR Oxford Biomedical Research Centre - Innovation & Evaluation Theme © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e768 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrew Erickson More articles by this author Emelie Berglund More articles by this author Mengxiao He More articles by this author Maja Marklund More articles by this author Reza Mirzazadeh More articles by this author Niklas Schultz More articles by this author Ludvig Bergenstråhle More articles by this author Linda Kvastad More articles by this author Alma Andersson More articles by this author Joseph Bergenstråhle More articles by this author Ludvig Larsson More articles by this author Alia Shamikh More articles by this author Elisa Basmaci More articles by this author Teresita Diaz De Ståhl More articles by this author Timothy Rajakumar More articles by this author Kim Thrane More articles by this author Andrew Ji More articles by this author Paul Khavari More articles by this author Firaz Tarish More articles by this author Anna Tanoglidi More articles by this author Jonas Maaskola More articles by this author Richard Colling More articles by this author Tuomas Mirtti More articles by this author Freddie C. Hamdy More articles by this author Dan Woodcock More articles by this author Thomas Helleday More articles by this author Ian Mills More articles by this author Alastair Lamb More articles by this author Joakim Lundeberg More articles by this author Expand All Advertisement PDF DownloadLoading ...