Renal Cancer – 10 years of FunGeST expertise at the service of clinicians

Group Leaders

Benoit BEUSELINCK

Oncologist in Leuven

Jessica ZUCMAN-ROSSI

MD, PhD

PUPHex Univeristy Paris 5

Actual Projects

J Zucman-Rossi (PUPH), B Beuselinck (PUPH Louvain)

Fundings: Inca

We aim to translate the molecular classification of clear cell renal cancer into genome based clinical trial int cooperation with Sautès-Fridman team at CRC and clinicans at HEGP and Louvain. We also search for biomarkers predicting response to anti-angiogenic thearapies.

Past Works

Recently, we described a molecular classification of clear cell renal cancer (ccRCCs) into four robust subgroups with distinctive characteristics on multi-omics analyses. These subgroups are defined by various levels of myc activation, angiogenic activation and immune response associated with outcome of metastatic ccRCC treated with sunitinib. This classification has future application in patient care, in particular to predict drug response.

Beseulinck et al, Clin Cancer Research 2015.

Publications

Fibroblast Growth Factor Receptor-2 Polymorphism rs2981582 is Correlated With Progression-free Survival and Overall Survival in Patients With Metastatic Clear-cell Renal Cell Carcinoma Treated With Sunitinib. Vanmechelen M, Lambrechts D, Van Brussel T, Verbiest A, Couchy G, Schöffski P, Dumez H, Debruyne PR, Lerut E, Machiels JP, Richard V, Albersen M, Verschaeve V, Oudard S, Méjean A, Wolter P, Zucman-Rossi J, Beuselinck B. Clin Genitourin Cancer. 2019 Apr;17(2):e235-e246. doi: 10.1016/j.clgc.2018.11.002. Epub 2018 Nov 16.

Polymorphisms in the Von Hippel-Lindau Gene Are Associated With Overall Survival in Metastatic Clear-Cell Renal-Cell Carcinoma Patients Treated With VEGFR Tyrosine Kinase Inhibitors. Verbiest A, Lambrechts D, Van Brussel T, Couchy G, Wozniak A, Méjean A, Lerut E, Oudard S, Verkarre V, Job S, de Reynies A, Machiels JP, Patard JJ, Zucman-Rossi J, Beuselinck B. Clin Genitourin Cancer. 2018 Aug;16(4):266-273. doi: 10.1016/j.clgc.2018.01.013.

Molecular Subtypes of Clear-cell Renal Cell Carcinoma are Prognostic for Outcome After Complete Metastasectomy. Verbiest A, Couchy G, Job S, Caruana L, Lerut E, Oyen R, de Reyniès A, Tosco L, Joniau S, Van Poppel H, Van Raemdonck D, Van Den Eynde K, Wozniak A, Zucman-Rossi J, Beuselinck B. Eur Urol. 2018 Oct;74(4):474-480. doi: 10.1016/j.eururo.2018.01.042. Epub 2018 Feb 17.

Pro-angiogenic gene expression is associated with better outcome on sunitinib in metastatic clear-cell renal cell carcinoma. Beuselinck B, Verbiest A, Couchy G, Job S, de Reynies A, Meiller C, Albersen M, Verkarre V, Lerut E, Méjean A, Patard JJ, Laguerre B, Rioux-Leclercq N, Schöffski P, Oudard S, Zucman-Rossi J. Acta Oncol. 2018 Apr;57(4):498-508. doi: 10.1080/0284186X.2017.1388927. Epub 2017 Nov 2.

Validation of VEGFR1 rs9582036 as predictive biomarker in metastatic clear-cell renal cell carcinoma patients treated with sunitinib. Beuselinck B, Jean-Baptiste J, Schöffski P, Couchy G, Meiller C, Rolland F, Allory Y, Joniau S, Verkarre V, Elaidi R, Lerut E, Roskams T, Patard JJ, Oudard S, Méjean A, Lambrechts D, Zucman-Rossi J. BJU Int. 2016 Dec;118(6):890-901. doi: 10.1111/bju.13585. Epub 2016 Aug 12.

RANK/OPG ratio of expression in primary clear-cell renal cell carcinoma is associated with bone metastasis and prognosis in patients treated with anti-VEGFR-TKIs. Beuselinck B, Jean-Baptiste J, Couchy G, Job S, De Reynies A, Wolter P, Théodore C, Gravis G, Rousseau B, Albiges L, Joniau S, Verkarre V, Lerut E, Patard JJ, Schöffski P, Méjean A, Elaidi R, Oudard S, Zucman-Rossi J. Br J Cancer. 2015 Nov 3;113(9):1313-22. doi: 10.1038/bjc.2015.352. Epub 2015 Oct 13.

Kidney cancer: Single nucleotide polymorphisms in mRCC-is their time up? Beuselinck B, Zucman-Rossi J. Nat Rev Urol. 2015 Aug;12(8):424-6. doi: 10.1038/nrurol.2015.149. Epub 2015 Jun 30. No

More publications

Brief history of the team

FunGeST “Functional genomics of solid tumors”, directed by Jessica Zucman-Rossi, was created in 2005, as Inserm U674, it was renewed in 2009 and 2014 as UMR1162, ranked “incontournable” by Inserm as a mixed structure endorsed by four entities: Inserm, Universities Paris Diderot, Paris Descartes and Paris Nord. It is currently located at the University Hematology Institute site in a building managed by the CEPH (Centre d’Etude du Polymorphisme Humain, Foundation Jean Dausset). Since January 2019, the lab take part of Centre de Recherche des Cordeliers Research Center – Inserm UMR S1138 as team 28.

Jessica Zucman-Rossi, is professor of Medicine in Oncology (PUPHex) at university Paris Descartes and HEGP, full time for research. She directed the Inserm U674, U1162 and UMRS1138 – team 28 since 2007, was chairman of the Inserm scientific committee devoted to Oncology, Genetics and Bioinformatics from 2012 to 2016. She is editor at Journal of Hepatology (IF=12.4), executive secretary of the International Liver Cancer Association (ILCA). She published 157 original papers and has an international recognition in the field of genomics of human cancers and more specifically in liver tumors. Since January 2019 Pr Zucman-Rossi-Rossi is the director of the Cordeliers Research Center.

Our missions

Our mission is to develop basic genomic approaches based on human tumors analyses to identify new mechanisms of tumorigenesis and to transfer this knowledge into biomarkers and therapeutic targets that could be introduced in clinical care. In particular, we aim to identify new genomic alterations and mechanisms of carcinogenesis. We also aim to identify new risk factors and genetic predispositions promoting the development of tumors. Our general strategy is based on the omic’s analyses of large cohorts of patients with liver tumors (benign and malignant), mesothelioma and clear cell renal carcinoma. The group was pioneer in the elucidation of the molecular classification of benign and malignant liver tumors. Then we perform (1) functional validation using cell and animal models and (2) we translate our findings into the clinics to improve surveillance, diagnosis, prognosis, treatment and follow-up of the patients.

Our task forces

The team include a total of 39 peoples organized in 5 groups with their founded projects:

“Functional Genomics of Liver tumors” led by Jessica Zucman-Rossi focusing in the characterization of genomic alterations in benign and malignant liver tumors, functional validation, identification of new risk factors and genetic predisposition and translation to the clinics.

“Functional Genomics of Mesothelioma” led by Didier Jean (CR1 Inserm) focusing on the pathogenesis of mesothelioma, search for new therapeutic targets with genomic approaches.

“Therapeutic Targets in liver tumors” led by Sandra Rebouissou (CR2 Inserm) focusing on the identification of therapeutic targets in liver tumors.

“Computational Cancer Genome Analysis” led by Eric Letouzé (CR2 Inserm) focusing on the development and application of innovative strategies for integrative genomic data analysis.

“Genomics of renal cancer” led by Jessica Zucman-Rossi & Benoit Beuselinck (Professor in Louvain)

Tag FunGeST

Functional Genomics of Renal Cancer