The dynamics of metastatic evolution in clear cell renal cell carcinoma (ccRCC) are complex. We report a case study where tumour heterogeneity resulting from clonal evolution is a frequent feature and could play a role in metastatic dissemination.
We used an integrative multiomics strategy combining genomic and transcriptomic data to classify fourteen specimens from spatially different areas of a kidney tumour and three non-primary sites including a vein thrombus and two adrenal metastases.
All sites were heterogeneous and polyclonal, each tumour site containing two different aggressive subclonal populations, with differentially expressed genes implicated in distinct biological functions. These are rare primary metastatic samples prior to any medical treatment, where we showed a multiple metastatic seeding of two subclonal populations.
Multiple interdependent lineages could be the source of metastatic heterogeneity in ccRCC. By sampling metastases, patients with resistance to therapies could benefit a combination of targeted therapies based on more than one aggressive clone.
- kidney neoplasms
- neoplasm metastasis
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Handling editor Runjan Chetty.
FC and NR-L contributed equally.
Contributors JD, AB, NR-L and FC analysed and interpreted the patient data. JD, MB, LC, FDu and M-AB-R performed genomic analyses. JD and BE performed DNA and RNA extraction. AL and JD performed VHL gene analyses. FDe, GV and KB supplied clinical support. All authors read and approved the final manuscript.
Funding The authors would like to thank the Ligue Régionale Contre Le Cancer, Institut national du cancer (INCa). FC and BE were supported by the Institut National de la Santé Et de la Recherche Médicale (INSERM), the Université de Rennes one and the Ecole des Hautes Etudes en Santé Publique (EHESP - School of Public Health).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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