title: Copy number gain of chromosome 3q is a recurrent event in patients with intraductal papillary mucinous neoplasm (IPMN) associated with disease progression.
abstract: Intraductal papillary mucinous neoplasm (IPMN) is the most common cystic preneoplastic lesion of pancreatic cancer. We used an approach coupling high resolution cytogenetic analysis (Affymetrix Oncoscan FFPE Array) with clinically-oriented bioinformatic interpretation of data to understand the most relevant alterations of precursor lesions at different stages to identify new diagnostic markers.
  
  
  
  We identified multiple copy number alterations, particularly in lesions with severe dysplasia, with 7 IPMN with low-intermediate dysplasia carrying a nearly normal karyotype and 13 IPMN with complex Karyotype (> 4 alterations), showing high grade dysplasia. A specific gain of chromosome arm 3q was found in IPMN with complex Karyotype (92%). This gain of 3q is particularly interesting for the presence of oncogenes such as PIK3CA, GATA2 and TERC that are part of pathways that deregulate cell growth and promote disease progression. Quantitative PCR and FISH analysis confirmed the data . Further demonstration of the overexpression of the PIK3CA gene supports the identification of this alteration as a possible biomarker in the early identification of patients with IPMN at higher risk for disease progression.
  
  
  
  High resolution cytogenetic analysis was performed in 20 formalin fixed paraffin embedded samples of IPMN by Oncoscan FFPE assay. Results were validated by qPCR and FISH analysis.
  
  
  
  The identification of these markers at an early stage of disease onset could help to identify patients at risk for cancer progression and new candidates for a more specific targeted therapy.
authors: Giorgio Prodi Cancer Research Centre, University of Bologna, Bologna, Italy.
authors: Sandra
authors: S
authors: Durante
authors: Department of Experimental, Diagnostic and Specialty Medicine University of Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
authors: Silvia
authors: S
authors: Vecchiarelli
authors: Giorgio Prodi Cancer Research Centre, University of Bologna, Bologna, Italy.
authors: Annalisa
authors: A
authors: Astolfi
authors: Department of Experimental, Diagnostic and Specialty Medicine University of Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
authors: Elisa
authors: E
authors: Grassi
authors: Department of Medical and Surgical Sciences, University of Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
authors: Riccardo
authors: R
authors: Casadei
authors: Pathology Unit, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
authors: Donatella
authors: D
authors: Santini
authors: Pathology Unit, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
authors: Riccardo
authors: R
authors: Panzacchi
authors: Department of Medical and Surgical Sciences, University of Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
authors: Claudio
authors: C
authors: Ricci
authors: Department of Medical and Surgical Sciences, "Lalla Seràgnoli" Hematology-Oncology Unit, University of Bologna, Bologna, Italy.
authors: Salvatore
authors: S
authors: Serravalle
authors: Giorgio Prodi Cancer Research Centre, University of Bologna, Bologna, Italy.
authors: Giuseppe
authors: G
authors: Tarantino
authors: DIBINEM-Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors: Mirella
authors: M
authors: Falconi
authors: DIBINEM-Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors: Gabriella
authors: G
authors: Teti
authors: Giorgio Prodi Cancer Research Centre, University of Bologna, Bologna, Italy.
authors: Valentina
authors: V
authors: Indio
authors: Department of Medical and Surgical Sciences, "Lalla Seràgnoli" Hematology-Oncology Unit, University of Bologna, Bologna, Italy.
authors: Andrea
authors: A
authors: Pession
authors: Department of Medical and Surgical Sciences, University of Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
authors: Francesco
authors: F
authors: Minni
authors: Giorgio Prodi Cancer Research Centre, University of Bologna, Bologna, Italy.|Department of Experimental, Diagnostic and Specialty Medicine University of Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
authors: Guido
authors: G
authors: Biasco
authors: Department of Experimental, Diagnostic and Specialty Medicine University of Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
authors: Mariacristina
authors: M
authors: Di Marco
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D002893:Chromosomes, Human, Pair 3; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D018450:Disease Progression; D006801:Humans; D007621:Karyotyping; D009154:Mutation; D060787:Neoplasm Grading; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor
keywords: IPMN; NGS; PDA; PIK3CA; chromosome 3