Array comparative genomic hybridization identifies novel potential therapeutic targets in cholangiocarcinoma

Authors


  • This paper was presented at the International Hepato-Pancreato-Biliary Association Annual Meeting, 18–22 April 2010, Buenos Aires, Argentina.

Siobhan C. McKay, Hepatopancreaticobiliary Surgery, Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK. Tel: + 44 208 383 2285. Fax: + 44 208 383 3963. E-mail: siobhan.mckay08@imperial.ac.uk

Abstract

Background:  Cholangiocarcinoma (CC) is a rare tumour with a dismal prognosis. As conventional medical management offers minimal survival benefit, surgery currently represents the only chance of cure. We evaluated DNA copy number (CN) alterations in CC to identify novel therapeutic targets.

Methods:  DNA was extracted from 32 CC samples. Bacterial artificial chromosome (BAC) array comparative genomic hybridization was performed using microarray slides containing 3400 BAC clones covering the whole human genome at distances of 1 Mb. Data were analysed within the R statistical environment.

Results:  DNA CN gains (89 regions) occurred more frequently than DNA CN losses (55 regions). Six regions of gain were identified in all cases on chromosomes 16, 17, 19 and 22. Twenty regions were frequently gained on chromosomes 1, 5, 7, 9, 11, 12, 16, 17, 19, 20 and 21. The BAC clones covering ERBB2, MEK2 and PDGFB genes were gained in all cases. Regions covering MTOR, VEGFR 3, PDGFA, RAF1, VEGFA and EGFR genes were frequently gained.

Conclusions:  We identified CN gains in the region of 11 useful molecular targets. Findings of variable gains in some regions in this and other studies support the argument for molecular stratification before treatment for CC so that treatment can be tailored to the individual patient.

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