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.
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.
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.
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