RT Journal Article
SR Electronic
T1 Multiple metastatic clones assessed by an integrative multiomics strategy in clear cell renal carcinoma: a case study
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 426
OP 430
DO 10.1136/jclinpath-2020-207326
VO 75
IS 6
A1 Dagher, Julien
A1 Brunot, Angelique
A1 Evrard, Bertrand
A1 Kammerer-Jacquet, Solene-Florence
A1 Beaumont, Marion
A1 Cornevin, Laurence
A1 Derquin, Fanny
A1 Verhoest, Gregory
A1 Bensalah, Karim
A1 Lespagnol, Alexandra
A1 Dugay, Frederic
A1 Belaud-Rotureau, Marc-Antoine
A1 Chalmel, Frédéric
A1 Rioux-Leclercq, Nathalie
YR 2022
UL http://jcp.bmj.com/content/75/6/426.abstract
AB 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.