Retrospective study testing next generation sequencing of selected cancer-associated genes in resected prostate cancer
| Autor: | Francesca Vignani, Ida Rapa, Enrico Bollito, Cristian Fiori, Susanna Cappia, Diletta Garrou, Mauro Papotti, Marco Volante, Consuelo Buttigliero, Marco Lo Iacono, Giorgio V. Scagliotti, Francesco Porpiglia, Valentina Monica, Marcello Tucci, Valentina Bertaglia |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology Biochemical recurrence Male medicine.medical_specialty medicine.medical_treatment Single-nucleotide polymorphism Bioinformatics Prognostic factors 03 medical and health sciences Prostate cancer 0302 clinical medicine Prostate Internal medicine Next generation sequencing medicine Biomarkers Tumor Humans Neoplasm Invasiveness Allele frequency Aged Neoplasm Staging Retrospective Studies Prostatectomy Genetic characterization Precision medicine business.industry Genetic Variation High-Throughput Nucleotide Sequencing Prostatic Neoplasms Retrospective cohort study medicine.disease Prognosis 030104 developmental biology medicine.anatomical_structure Tumor progression 030220 oncology & carcinogenesis Disease Progression Neoplasm Grading Neoplasm Recurrence Local business Research Paper Follow-Up Studies |
| Zdroj: | Oncotarget |
| Popis: | // Marco Lo Iacono 1, * , Consuelo Buttigliero 1, * , Valentina Monica 1, * , Enrico Bollito 1 , Diletta Garrou 1 , Susanna Cappia 1 , Ida Rapa 1 , Francesca Vignani 1 , Valentina Bertaglia 1 , Cristian Fiori 1 , Mauro Papotti 1 , Marco Volante 1 , Giorgio V. Scagliotti 1 , Francesco Porpiglia 1 , Marcello Tucci 1 1 University of Turin, Department of Oncology, Orbassano, Italy * All these Authors equally contributed to the experimental study Correspondence to: Consuelo Buttigliero, e-mail: consuelo.buttigliero@gmail.com 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. |
| Databáze: | OpenAIRE |
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