iPSC-Derived Embryoid Bodies as Models of c-Met-Mutated Hereditary Papillary Renal Cell Carcinoma
Authors: Frank Griscelli
Sophie Ferlicot
Jin Wook Hwang
Adlen Foudi
Annelise Bennaceur-Griscelli
Ali G Turhan
Julien Loisel-Duwattez
Christophe Desterke
Stephane Richard
Olivier F√©raud
Virginie Verkarre
Jean Jacques Patard
Journal: International Journal of Molecular Sciences (2019)
Discipline: CHEMISTRY
Keywords: Hereditary papillary renal cell carcinoma; c-Met mutation; induced pluripotent stem cell; kidney cancer organoids.
Affiliations: INSERM UMR-S 935 and ESTeam Paris Sud, Universit√© Paris Sud, 94800 Villejuif, France. ., R√©seau National de R√©f√©rence pour Cancers Rares de l'Adulte PREDIR, labellis√© par l'INCa, et Service d'Urologie, AP-HP, H√¥pital Bic√™tre, 94270 Le Kremlin-Bic√™tre, France; G√©n√©tique Oncologique EPHE, PSL Universit√©, INSERM UMR 1186, Gustave Roussy, Facult√© de M√©decine et Universit√© Paris-Sud, 94800 Villejuif, France. ., INSERM, UMR 1186, Gustave Roussy, Paris-Sud University, Paris-Saclay University, 94800 Villejuif, France. ., Service d'Anatomie Pathologique, H√¥pital Europ√©en Georges Pompidou, AP-HP, 75015 Paris, France. ., Service d'Urologie, Centre Hospitalier de Mont de Marsan, 40024 Mont de Marsan, France. ., INSERM U1195, Universit√© Paris Sud, Facult√© de M√©decine, APHP, Service de Neurologie, H√¥pital Bic√™tre, 94276 le Kremlin Bic√™tre, France. .

Abstract:  Hereditary cancers with cancer-predisposing mutations represent unique models of human oncogenesis, as a driving oncogenic event is present in germline. Currently, there are no satisfactory models to study these malignancies. We report the generation of IPSC from the somatic cells of a patient with hereditary c-met-mutated papillary renal cell carcinoma (PRCC). From these cells we have generated spontaneous aggregates organizing in structures which expressed kidney markers such as PODXL and Six2. These structures expressed PRCC markers both in vitro and in vivo in NSG mice. Gene-expression profiling showed striking molecular similarities with signatures found in a large cohort of PRCC tumor samples. This analysis, applied to primary cancers with and without c-met mutation, showed overexpression of the BHLHE40 and KDM4C only in the c-met-mutated PRCC tumors, as predicted by c-met-mutated embryoid bodies transcriptome. These data therefore represent the first proof of concept of "hereditary renal cancer in a dish" model using c-met-mutated iPSC-derived embryoid bodies, opening new perspectives for discovery of novel predictive progression markers and for drug-screening for future precision-medicine strategies. 

Retracted: No

PubPeer comments:
 This paper and  Modeling and control for nonlinear structural systems via a NN-based approach ([Chen, 2009] ) both simulate the responses of building stabilisation, using the Chi-Chi Taiwan earthquake as input. The results are identical, which poses all sorts of questions, as the models and algorithms for stabilisation are quite different.  UPDATE: In  Stability analysis and robustness design of nonlinear systems: An NN-based approach ([Chen, 2011] , the author again used the Chi-Chi earthquake as input for a simulation of an algorithm for building stabilisation. Again, **the results were identical**.  UPDATE #2. Fig 4 from  Robustness design of time-delay fuzzy systems using fuzzy Lyapunov method ([Yeh, Chen Chen 2008] ):  ,