• Daniele Fanale, Juan Lucio Iovanna, Ezequiel Luis Calvo, Patrice Berthezene, Pascal Belleau, Jean Charles Dagorn, Giuseppe Bronte, Giuseppe Cicero, Viviana Bazan, Christian Rolfo, Daniele Santini, and Antonio Russo.
• University of Palermo, Department of Surgical, Oncological and Stomatological Sciences, Section of Medical Oncology , Via del Vespro 129, 90127 Palermo , Italy +39 091 6552500 ; +011 39 091 6554529 ; antonio.russo@usa.net.
• Expert Opin. Ther. Targets. 2014 Aug 1;18(8):841-50.

ObjectiveThe vast majority of pancreatic cancers occurs sporadically. The discovery of frequent variations in germline gene copy number can significantly influence the expression levels of genes that predispose to pancreatic adenocarcinoma. We prospectively investigated whether patients with sporadic pancreatic adenocarcinoma share specific gene copy number variations (CNVs) in their germline DNA.Patients And MethodsDNA samples were analyzed from peripheral leukocytes from 72 patients with a diagnosis of sporadic pancreatic adenocarcinoma and from 60 controls using Affymetrix 500K array set. Multiplex ligation-dependent probe amplification (MLPA) assay was performed using a set of self-designed MLPA probes specific for seven target sequences.ResultsWe identified a CNV-containing DNA region associated with pancreatic cancer risk. This region shows a deletion of 1 allele in 36 of the 72 analyzed patients but in none of the controls. This region is of particular interest since it contains the YTHDC2 gene encoding for a putative DNA/RNA helicase, such protein being frequently involved in cancer susceptibility. Interestingly, 82.6% of Sicilian patients showed germline loss of one allele.ConclusionsOur results suggest that the YTHDC2 gene could be a potential candidate for pancreatic cancer susceptibility and a useful marker for early detection as well as for the development of possible new therapeutic strategies.

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