Oncotarget

Research Papers:

Retrospective study testing next generation sequencing of selected cancer-associated genes in resected prostate cancer

Marco Lo Iacono _, Consuelo Buttigliero, Valentina Monica, Enrico Bollito, Diletta Garrou, Susanna Cappia, Ida Rapa, Francesca Vignani, Valentina Bertaglia, Cristian Fiori, Mauro Papotti, Marco Volante, Giorgio V. Scagliotti, Francesco Porpiglia and Marcello Tucci

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Oncotarget. 2016; 7:14394-14404. https://doi.org/10.18632/oncotarget.7343

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Abstract

Marco Lo Iacono1,*, Consuelo Buttigliero1,*, Valentina Monica1,*, Enrico Bollito1, Diletta Garrou1, Susanna Cappia1, Ida Rapa1, Francesca Vignani1, Valentina Bertaglia1, Cristian Fiori1, Mauro Papotti1, Marco Volante1, Giorgio V. Scagliotti1, Francesco Porpiglia1, Marcello Tucci1

1University of Turin, Department of Oncology, Orbassano, Italy

*All these Authors equally contributed to the experimental study

Correspondence to:

Consuelo Buttigliero, e-mail: [email protected]

Keywords: next generation sequencing, prostate cancer, precision medicine, genetic characterization, prognostic factors

Received: November 17, 2015    Accepted: January 25, 2016    Published: February 12, 2016

ABSTRACT

Purpose: Prostate cancer (PCa) has a highly heterogeneous outcome. Beyond Gleason Score, Prostate Serum Antigen and tumor stage, nowadays there are no biological prognostic factors to discriminate between indolent and aggressive tumors.

The most common known genomic alterations are the TMPRSS-ETS translocation and mutations in the PI3K, MAPK pathways and in p53, RB and c-MYC genes.

The aim of this retrospective study was to identify by next generation sequencing the most frequent genetic variations (GVs) in localized and locally advanced PCa underwent prostatectomy and to investigate their correlation with clinical-pathological variables and disease progression.

Results: Identified non-synonymous GVs included TP53 p.P72R (78% of tumors), two CSFR1 SNPs, rs2066934 and rs2066933 (70%), KDR p.Q472H (67%), KIT p.M541L (28%), PIK3CA p.I391M (19%), MET p.V378I (10%) and FGFR3 p.F384L/p.F386L (8%). TP53 p.P72R, MET p.V378I and CSFR1 SNPs were significantly associated with the HI risk group, TP53 and MET variations with T≥T2c. FGFR3 p.F384L/p.F386L was correlated with T≤T2b. MET p.V378I mutation, detected in 20% of HI risk patients, was associated with early biochemical recurrence.

Experimental design: Nucleic acids were obtained from tissue samples of 30 high (HI) and 30 low-intermediate (LM) risk patients, according to D’Amico criteria. Genomic DNA was explored with the Ion_AmpliSeq_Cancer_Hotspot_Panel_v.2 including 50 cancer-associated genes. GVs with allelic frequency (AF) ≥10%, affecting protein function or previously associated with cancer, were correlated with clinical-pathological variables.

Conclusion: Our results confirm a complex mutational profile in PCa, supporting the involvement of TP53, MET, FGFR3, CSF1R GVs in tumor progression and aggressiveness.


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