Distinct molecular profiles and shared drug vulnerabilities in pancreatic metastases of renal cell carcinoma.

Autor: Roos-Mattila M; Department of Surgery, Helsinki University Hospital, Helsinki, Finland. matilda.roos-mattila@helsinki.fi.; Translational Cancer Medicine Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland. matilda.roos-mattila@helsinki.fi.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland. matilda.roos-mattila@helsinki.fi., Kallio P; Translational Cancer Medicine Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland., Luck TJ; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Institute for Molecular Medicine Finland -FIMM, Helsinki Institute for Life Sciences -HiLIFE, University of Helsinki, Helsinki, Finland., Polso M; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Institute for Molecular Medicine Finland -FIMM, Helsinki Institute for Life Sciences -HiLIFE, University of Helsinki, Helsinki, Finland., Kumari R; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Institute for Molecular Medicine Finland -FIMM, Helsinki Institute for Life Sciences -HiLIFE, University of Helsinki, Helsinki, Finland., Mikkonen P; Institute for Molecular Medicine Finland -FIMM, Helsinki Institute for Life Sciences -HiLIFE, University of Helsinki, Helsinki, Finland., Välimäki K; Institute for Molecular Medicine Finland -FIMM, Helsinki Institute for Life Sciences -HiLIFE, University of Helsinki, Helsinki, Finland., Malmstedt M; Department of Surgery, Helsinki University Hospital, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; ONCOSYS Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Ellonen P; Institute for Molecular Medicine Finland -FIMM, Helsinki Institute for Life Sciences -HiLIFE, University of Helsinki, Helsinki, Finland., Pellinen T; Institute for Molecular Medicine Finland -FIMM, Helsinki Institute for Life Sciences -HiLIFE, University of Helsinki, Helsinki, Finland., Heckman CA; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Institute for Molecular Medicine Finland -FIMM, Helsinki Institute for Life Sciences -HiLIFE, University of Helsinki, Helsinki, Finland., Mustonen H; Department of Surgery, Helsinki University Hospital, Helsinki, Finland.; Translational Cancer Medicine Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland., Puolakkainen PA; Department of Surgery, Helsinki University Hospital, Helsinki, Finland.; Translational Cancer Medicine Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland., Alitalo K; Translational Cancer Medicine Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Wihuri Research Institute, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland., Kallioniemi O; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Institute for Molecular Medicine Finland -FIMM, Helsinki Institute for Life Sciences -HiLIFE, University of Helsinki, Helsinki, Finland.; Science for Life Laboratory (SciLifeLab), Department of Oncology and Pathology, Karolinska Institutet, Solna, 17165, Sweden., Mirtti T; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; ONCOSYS Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; HUS Diagnostic Center, Department of Pathology, Helsinki University Hospital, Helsinki, Finland., Rannikko AS; Department of Surgery, Helsinki University Hospital, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; ONCOSYS Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Pietiäinen VM; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.; Institute for Molecular Medicine Finland -FIMM, Helsinki Institute for Life Sciences -HiLIFE, University of Helsinki, Helsinki, Finland., Seppänen HE; Department of Surgery, Helsinki University Hospital, Helsinki, Finland.; Translational Cancer Medicine Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Oct 20; Vol. 7 (1), pp. 1355. Date of Electronic Publication: 2024 Oct 20.
DOI: 10.1038/s42003-024-07004-9
Abstrakt: Clear-cell renal cell carcinoma (ccRCC) is the most common origin of pancreatic metastases (PM). Distinct genomic aberrations, favorable prognosis, and clinical observations on high angiogenesis, and succeeding tyrosine kinase inhibitor (TKI) sensitivity have been reported in PM-ccRCC. However, no functional or single-cell studies have been conducted thus far. We recruited five PM-ccRCC patients and investigated the genomic, single-cell transcriptomic, and drug sensitivity profiles of their patient-derived cells (PDCs). The PM depicted both expected and novel genomic alterations. Further, the transcriptomics differed from both primary and metastatic ccRCC, with upregulations of the PI3K/mTOR and - supporting the clinical observations - angiogenesis pathways. Data integration at pathway level showed that transcriptomics explained drug sensitivities the best. Accordingly, PM-ccRCC PDCs shared sensitivity to many PI3K/mTOR inhibitors. Altogether, we show distinct genomic and transcriptomic signatures in PM-ccRCC, highlight the superiority of transcriptomics in interpreting drug sensitivities, and encourage the use of TKIs and PI3K/mTOR inhibitors in PM-ccRCC.
(© 2024. The Author(s).)
Databáze: MEDLINE
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