Pd09-08 Spatial Transcriptomic Clonal Deconvolution Identifies the ‘Lethal Clone’ in Prostate Cancer as Defined by Ability to Metastasize to Lymph Nodes

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (PD09)1 May 2024PD09-08 SPATIAL TRANSCRIPTOMIC CLONAL DECONVOLUTION IDENTIFIES THE 'LETHAL CLONE' IN PROSTATE CANCER AS DEFINED BY ABILITY TO METASTASIZE TO LYMPH NODES Wencheng Yin, Sandy Figiel, Mengxiao He, Renuka Teague, Thineskrishna Anbarasan, Nithesh Ranasinha, Reema Singh, Ninu Poulose, Dimitrios Doultsinos, Sophia Abusamra, Andrew Erickson, Massimo Loda, Clare Verrill, Richard Colling, Pelvender Gill, Richard Bryant, Olivier Cussenot, Freddie Hamdy, Dan Woodcock, Ian Mills, Joakim Lundeberg, and Alastair Lamb Wencheng YinWencheng Yin , Sandy FigielSandy Figiel , Mengxiao HeMengxiao He , Renuka TeagueRenuka Teague , Thineskrishna AnbarasanThineskrishna Anbarasan , Nithesh RanasinhaNithesh Ranasinha , Reema SinghReema Singh , Ninu PouloseNinu Poulose , Dimitrios DoultsinosDimitrios Doultsinos , Sophia AbusamraSophia Abusamra , Andrew EricksonAndrew Erickson , Massimo LodaMassimo Loda , Clare VerrillClare Verrill , Richard CollingRichard Colling , Pelvender GillPelvender Gill , Richard BryantRichard Bryant , Olivier CussenotOlivier Cussenot , Freddie HamdyFreddie Hamdy , Dan WoodcockDan Woodcock , Ian MillsIan Mills , Joakim LundebergJoakim Lundeberg , and Alastair LambAlastair Lamb View All Author Informationhttps://doi.org/10.1097/01.JU.0001008572.33286.63.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) epitomises intratumoural heterogeneity, a phenomenon that has hindered accurate risk stratification & treatment. A distinctive feature of this heterogeneity is the frequent occurrence of copy number alterations acquired by dividing cells, which can be used to define clonal heritage. The precise contribution of local cancer clones to lethal metastatic PCa is unclear. This study leveraged spatial transcriptomics technology to infer clonal genomic identity in PCa to identify regions of primary tumour that can metastasize to lymph nodes. METHODS: We collated FFPE samples from primary & nodal metastatic tissue of 4 patients recruited in trial (ISRCTN10046036). We performed spatial transcriptomics (Visium v2), processed fastq files using SpaceRanger & analysed with our published protocol (github.com/aerickso/SpatialInferCNV). Each section contains around 5,000 (6.5 mm2) or 14,000 (11 mm2) spots of 55 µm diameter with meticulous histological annotation by pathologist. We show the clonal relationships, location & distribution throughout prostate & nodal environment. RESULTS: We identified 11 clonal subtypes on epithelial tissue. We show the distinct features of specific clones which exist in both primary & lymph nodes metastases ("X clones") alongside their clonal ancestry as a phylogenetic tree. Interestingly, we observed subclonal events within the lymph nodes & evidence for polyclonal colonisation of lymph nodes at distinct time points in the evolution of primary disease. Specifically, we observed Chr10q loss, the location of PTEN, was an early event in the clonal ancestry of lethal disease. PTEN is a well-known tumour suppressor gene, the loss of which causes chromosomal instability. Chr8 gain/loss was an important later event in the transition to migratory behaviour possibly due to phenotypic versatility resulting from amplification of genes such as c-Myc. CONCLUSIONS: For the first time, we detail the clonal heterogeneity in PCa, with direct linkage to nodal metastases. Spatial transcriptomics with careful case selection & highly granular pathology, is a powerful tool to decipher clonal hierarchies & trace the evolution of lethal disease. This has important implications for risk stratification & treatment selection in PCa. Download PPT Source of Funding: The present work was supported by Cancer Research UK (CRUK), Hanson Trust Research, the John Black Charitable Foundation, Prostate Cancer Foundation, NIHR Oxford Biomedical Research Centre, European Research Council, Swedish Society for Cancer Research © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e182 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Wencheng Yin More articles by this author Sandy Figiel More articles by this author Mengxiao He More articles by this author Renuka Teague More articles by this author Thineskrishna Anbarasan More articles by this author Nithesh Ranasinha More articles by this author Reema Singh More articles by this author Ninu Poulose More articles by this author Dimitrios Doultsinos More articles by this author Sophia Abusamra More articles by this author Andrew Erickson More articles by this author Massimo Loda More articles by this author Clare Verrill More articles by this author Richard Colling More articles by this author Pelvender Gill More articles by this author Richard Bryant More articles by this author Olivier Cussenot More articles by this author Freddie Hamdy More articles by this author Dan Woodcock More articles by this author Ian Mills More articles by this author Joakim Lundeberg More articles by this author Alastair Lamb More articles by this author Expand All Advertisement PDF downloadLoading ...