ESMO Virtual Congress 2020: An Integrated Study of Spatial Dynamics and Genomic Alterations in Renal Cell Carcinoma Evolution

(UroToday.com) The TRACERx (TRAcking Cancer Evolution through therapy (Rx)) consortium aims to utilize cutting edge biologic techniques and analysis to uncover mechanisms of cancer evolution as well as explore intratumoral heterogeneity and its association with therapy response. In a 2018 paper, the consortium published genomic data from 1,206 primary tumor biopsies from 101 patients with clear cell renal cell carcinoma, highlighting substantial genetic diversity and complexity across and within tumors.1 In this presentation, Dr. Zhao reports analysis integrating spatial information with genomic data to further explore RCC evolution.


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Tumor centers were enriched for more aggressive features such as higher proliferation rate, necrosis, burden of somatic copy number alteration, Fuhrmann grade 4 regions, and subclones also found in metastases. This may be a consequence of relative hypoxia and subsequent stress at the tumor center.

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The authors also explored spatial patterns of clonal expansion using phylogenetic reconstructions of tumor evolution. They found that most adjacent regions had genomic alterations consistent with contiguous clonal expansion, that is, from a founder clone, a nearby biopsy had alterations consistent with that nearby biopsy being a “child clone”, and the next nearest biopsy to that had genomic patterns consistent with it being a “grandchild clone” and so on. However, a few cases of dispersed clonal expansion were observed, where a child clone was found to be surrounded by genomically distinct contiguous expansion clones, as shown in the figure below. The implications and frequency of this dispersed clonal expansion model require further study but highlight the potential of spatial genomics in further understanding patterns of tumor evolution in renal cell carcinoma.

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Presented by: Yue Zhao, MBBS, MSc, PhD candidate at the Francis Crick Institute, United Kingdom

Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, 2020 European Society for Medical Oncology Virtual Congress (#ESMO20), September 19th-September 21st, 2020.

References:

  1. Samra Turajlic, Hang Xu, Kevin Litchfield, James Larkin, Charles Swanton et al. Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal. 2018. DOI:https://doi.org/10.1016/j.cell.2018.03.043
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EAU 2018: Results from the TRACERx Renal Study: Deterministic Routes to Tumor Progression in Clear Cell Renal Cell Carcinoma