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

M. Fiorentino, E. Gruppioni, F. Massari, F. Giunchi, A. Altimari, C. Ciccarese, D. Bimbatti, A. Scarpa, R. Iacovelli, C. Porta, S. Virinder, G. Tortora, W. Artibani, R. Schiavina, A. Ardizzoni, M. Brunelli, S. Knuutila, G. Martignoni

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)7328-7335
Number of pages8
Issue number5
Publication statusPublished - Jan 31 2017


  • Pathology Section
  • VHL
  • metastatic disease
  • next generation sequencing
  • renal cell carcinoma
  • target therapy


Dive into the research topics of 'Wide spetcrum mutational analysis of metastatic renal cell cancer: a retrospective next generation sequencing approach'. Together they form a unique fingerprint.

Cite this