Abstract 3881: Genetic alterations in intrahepatic cholangiocarcinoma- revealed by array CGH, SKY and gene expression microarray

Abstract

Cholangiocarcinoma (CCA) is an adenocarcinoma of the biliary tract, which is considered to be an incurable and rapidly lethal disease. A major problem with CCA surveillance is the lack of reliable biomarkers, therefore, still less no significant aspects of client-centered therapy in clinical treatment so far. Here, we established a 25th week thioacetamide (TAA)-induced cholangiocarcinoma rat cell line model named Chang Gung CCA (CGCCA), aim to figure out the early alterations of cytogenetics, molecular and protein expressed characteristics of CCA. Array comparative genomic hybridization (aCGH) and Spectral karyotyping (SKY), gene expression microarray and immunohistochemistry were performed on either rat CCA tissues or CGCCA cell line in this study. Our results showed complicated alterations of genetic gain or loss on different chromosomal regions could be observed. The data compared with the gene expression profile, thirty-three genes aberrations could be further identified; for example, tumor metastasis-related genes ANXA1 and CLCA3, the genes MMP7 and MMP12 are related with tumor invasion, and proliferation-related genes PKM2 and OSMR have been pinpointed; The number of chromosome ranging between 50 to 56 diplody (2n); despite the apparently high incidence of chromosomal translocation was revealed by cytogenetic analyses, ring and/or giant rod marker chromosomes were detected in almost every CGCCA cells, and the genetic materials are mainly included chromosomes 4 and 8. Herein, we concluded ANXA1, CLCA3, MMP7, MMP12, PKM2 and OSMR genes could be considered as potential biomarkers for the risk of disease. Supernumerary ring or giant rod marker chromosomes could also be considered as a characteristic may be involved in the late stage of CCA. However, the genes involved in the tumorigenesis should be further investigated the function of the genes. In order to verify the clinical significance and potentially to be as therapeutic targets in the future, to confirm onto a series of human CCA tissues are necessary. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3881. doi:10.1158/1538-7445.AM2011-3881