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Spatial visualisation of tumour clones © Nature

Spatial clonal biology

This work is funded by Cancer Research UK as the SPACE study “Spatial Prostate Assessment and the Circulating Environment”, through a Clinician Scientist Fellowship awarded to Alastair Lamb. Cancer tissue is three-dimensional with complex variations and traditional approaches have required scientists to break up the tissue and analyse genetic changes ‘in bulk’. This is a particular issue in prostate cancer which, although it affects tens of thousands of men every year, is very variable between different patients and even within individual prostates. Our prostate group have used spatial transcriptomics to create cross-sectional clonal maps of whole prostates, including areas of both healthy and cancerous tissue (REF). This work, led by Andrew Erickson, has enabled us to define clonal dynamics within prostate glandular structure revealing previously unknown findings about copy number mutations occurring in histological benign prostate tissue, and about the subclonal composition of malignant prostate cancer. We have established a robust pipeline for spatial transcriptomic work led by Sandy Figiel (using Visium technology, 10X Genomics), from operating theatre, through pathology lab, wet lab, sequencing facility and data analysis. This work is dependent on high quality computational biology led by Wencheng Ying, with oversight from Dan Woodcock. In this work we collaborate closely with Joakim Lundeberg’s group (Science for Life Laboratory, Stockholm). Our next steps are to identify the ‘lethal clone’ within primary prostate cancer by linkage to sites of early metastatic disease and prostate cancer cells in circulation (REF).  We also work with diagnostic prostate biopsy material with a particular focus on identifying important cancer clones, at the first tissue sampling point in the prostate cancer pathway, which may escape the prostate prior to radical treatment, or evade hormonal manipulation (REF).