mutational profiling of kinases in human tumours of pancreatic origin identifies candidate cancer genes in ductal and ampulla of vater carcinomas激酶在人类肿瘤的突变分析胰腺来源识别候选癌基因在导管和肝胰管壶腹癌.pdfVIP

Mutational Profiling of Kinases in Human Tumours of Pancreatic Origin Identifies Candidate Cancer Genes in Ductal and Ampulla of Vater Carcinomas 1 1 2 3 3 4 Vincenzo Corbo , Rossana Ritelli , Stefano Barbi , Niccola Funel , Daniela Campani , Alberto Bardelli , Aldo Scarpa1,2* 1 ARC-NET Research Center, University of Verona, Policlinico G.B. Rossi, Verona, Italy, 2 Department of Pathology, University of Verona, Policlinico G.B. Rossi, Verona, Italy, 3 Department of Pathology, University of Pisa, Pisa, Italy, 4 Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy Abstract Background: Protein kinases are key regulators of cellular processes (such as proliferation, apoptosis and invasion) that are often deregulated in human cancers. Accordingly, kinase genes have been the first to be systematically analyzed in human tumors leading to the discovery that many oncogenes correspond to mutated kinases. In most cases the genetic alterations translate in constitutively active kinase proteins, which are amenable of therapeutic targeting. Tumours of the pancreas are aggressive neoplasms for which no effective therapeutic strategy is currently available. Methodology/Principal Findings: We conducted a DNA-sequence analysis of a selected set of 35 kinase genes in a panel of 52 pancreatic exocrine neoplasms, including 36 pancreatic ductal adenocarcinoma, and 16 ampulla of Vater cancer. Among other changes we found somatic mutations in ATM, EGFR, EPHA3, EPHB2, and KIT, none of which was previously described in cancers. Conclusions/Significance: Although the alterations identified require further experimental evaluation, the localization within defined p