Wide spetcrum mutational analysis of metastatic renal cell cancer : a retrospective next generation sequencing approach

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Fiorentino , M , Gruppioni , E , Massari , F , Giunchi , F , Altimari , A , Ciccarese , C , Bimbatti , D , Scarpa , A , Iacovelli , R , Porta , C , Virinder , S , Tortora , G , Artibani , W , Schiavina , R , Ardizzoni , A , Brunelli , M , Knuutila , S & Martignoni , G 2017 , ' Wide spetcrum mutational analysis of metastatic renal cell cancer : a retrospective next generation sequencing approach ' , Oncotarget , vol. 8 , no. 5 , pp. 7328-7335 . https://doi.org/10.18632/oncotarget.12551

Title: Wide spetcrum mutational analysis of metastatic renal cell cancer : a retrospective next generation sequencing approach
Author: Fiorentino, Michelangelo; Gruppioni, Elisa; Massari, Francesco; Giunchi, Francesca; Altimari, Annalisa; Ciccarese, Chiara; Bimbatti, Davide; Scarpa, Aldo; Iacovelli, Roberto; Porta, Camillo; Virinder, Sarhadi; Tortora, Giampaolo; Artibani, Walter; Schiavina, Riccardo; Ardizzoni, Andrea; Brunelli, Matteo; Knuutila, Sakari; Martignoni, Guido
Contributor: University of Helsinki, Medicum
Date: 2017
Language: eng
Number of pages: 8
Belongs to series: Oncotarget
ISSN: 1949-2553
URI: http://hdl.handle.net/10138/177035
Abstract: Renal cell cancer (RCC) is characterized by histological and molecular heterogeneity that may account for variable response to targeted therapies. We evaluated retrospectively with a next generation sequencing (NGS) approach using a pre-designed cancer panel the mutation burden of 32 lesions from 22 metastatic RCC patients treated with at least one tyrosine kinase or mTOR inhibitor. We identified mutations in the VHL, PTEN, JAK3, MET, ERBB4, APC, CDKN2A, FGFR3, EGFR, RB1, TP53 genes. Somatic alterations were correlated with response to therapy. Most mutations hit VHL1 (31,8%) followed by PTEN (13,6%), JAK3, FGFR and TP53 (9% each). Eight (36%) patients were wild-type at least for the genes included in the panel. A genotype concordance between primary RCC and its secondary lesion was found in 3/6 cases. Patients were treated with Sorafenib, Sunitinib and Temsirolimus with partial responses in 4 (18,2%) and disease stabilization in 7 (31,8%). Among the 4 partial responders, 1 (25%) was wild-type and 3 (75%) harbored different VHL1 variants. Among the 7 patients with disease stabilization 2 (29%) were wild-type, 2 (29%) PTEN mutated, and single patients (14% each) displayed mutations in VHL1, JAK3 and APC/CDKN2A. Among the 11 non-responders 7 (64%) were wild-type, 2 (18%) were p53 mutated and 2 (18%) VHL1 mutated. No significant associations were found among RCC histotype, mutation variants and response to therapies. In the absence of predictive biomarkers for metastatic RCC treatment, a NGS approach may address single patients to basket clinical trials according to actionable molecular specific alterations.
Subject: renal cell carcinoma
next generation sequencing
target therapy
metastatic disease
VHL
Pathology Section
TARGETED THERAPY
CARCINOMA
3111 Biomedicine
3122 Cancers
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