| Autor: |
Gattolliat CH; Oncogenetics Laboratory, EPHE, PSL Research University, 75014 Paris, France., Couvé S; Oncogenetics Laboratory, EPHE, PSL Research University, 75014 Paris, France., Meurice G; Bioinformatic Platform, 94800 Villejuif, France., Oréar C; Genomic Platform, Gustave Roussy, 94800 Villejuif, France., Droin N; Genomic Platform, Gustave Roussy, 94800 Villejuif, France., Chiquet M; Oncogenetics Laboratory, EPHE, PSL Research University, 75014 Paris, France., Ferlicot S; INSERM, UMR 1186, Gustave Roussy, Paris-Sud University, Paris-Saclay University, 94800 Villejuif, France., Verkarre V; PREDIR INCa, Department of Urology, AP-HP, Bicêtre Hospital, 94270 Le Kremlin-Bicêtre, France., Vasiliu V; Department of Pathological Anatomy, Necker Hospital, 75015 Paris, France., Molinié V; Department of Pathological Anatomy and Cytology, Saint Joseph Hospital, 75014 Paris, France., Méjean A; PREDIR INCa, Department of Urology, AP-HP, Bicêtre Hospital, 94270 Le Kremlin-Bicêtre, France., Dessen P; Bioinformatic Platform, 94800 Villejuif, France., Giraud S; PREDIR INCa, Department of Urology, AP-HP, Bicêtre Hospital, 94270 Le Kremlin-Bicêtre, France., Bressac-De-Paillerets B; INSERM, UMR 1186, Gustave Roussy, Paris-Sud University, Paris-Saclay University, 94800 Villejuif, France., Gardie B; Oncogenetics Laboratory, EPHE, PSL Research University, 75014 Paris, France., Tean Teh B; National Cancer Centre, Duke Graduate Medical School, Cancer Science Institute of Singapore, Institute of Molecular and Cellular Biology, Singapore 138673, Singapore., Richard S; Oncogenetics Laboratory, EPHE, PSL Research University, 75014 Paris, France., Gad S; Oncogenetics Laboratory, EPHE, PSL Research University, 75014 Paris, France. |
| Abstrakt: |
Von Hippel-Lindau (VHL) disease is a rare autosomal dominant syndrome that is the main cause of inherited clear-cell renal cell carcinoma (ccRCC), which generally occurs in the form of multiple recurrent synchronized tumors. Affected patients are carriers of a germline mutation in the VHL tumor suppressor gene. Somatic mutations of this gene are also found in sporadic ccRCC and numerous pan-genomic studies have reported a dysregulation of microRNA (miRNA) expression in these sporadic tumors. In order to investigate the molecular mechanisms underlying the pathogenesis of VHL-associated ccRCC, particularly in the context of multiple tumors, the present study characterized the mRNA and miRNA transcriptome through an integrative analysis compared with sporadic renal tumors. In the present study, two series of ccRCC samples were used. The first set consisted of several samples from different tumors occurring in the same patient, for two independent patients affected with VHL disease. The second set consisted of 12 VHL-associated tumors and 22 sporadic ccRCC tumors compared with a pool of normal renal tissue. For each sample series, an expression analysis of miRNAs and mRNAs was conducted using microarrays. The results indicated that multiple tumors within the kidney of a patient with VHL disease featured a similar pattern of miRNA and gene expression. In addition, the expression levels of miRNA were able to distinguish VHL-associated tumors from sporadic ccRCC, and it was identified that 103 miRNAs and 2,474 genes were differentially expressed in the ccRCC series compared with in normal renal tissue. The majority of dysregulated genes were implicated in 'immunity' and 'metabolism' pathways. Taken together, these results allow a better understanding of the occurrence of ccRCC in patients with VHL disease, by providing insights into dysregulated miRNA and mRNA. In the set of patients with VHL disease, there were few differences in miRNA and mRNA expression, thus indicating a similar molecular evolution of these synchronous tumors and suggesting that the same molecular mechanisms underlie the pathogenesis of these hereditary tumors. |
