Mutations of KRAS and TP53 in a Minor Proportion of Opisthorchis Viverrini-Associated Cholangiocarcinomas in a Hamster Model


Background/Aims KRAS oncogene and TP53 tumor suppressor gene have been known as common genesinvolving in many cancers including cholangiocarcinoma (CCC). Activation of these genes could lead touncontrolled proliferation and cancer ultimately. The aim of this study was to investigate mutation of KRASexon 1 and TP53 exon 5-8 in Opisthorchis viverrini (OV)-induced cholangiocarcinoma (CCA) in a hamster model.
Methods: Twenty-seven CCAs were obtained from Syrian golden hamsters induced by OV infection and Nnitrosodimethylnitrosamine(N-NDDM) administration. The tumor tissues were processed for histopathology.Genomic DNA extracted from paraffin sections by microdissection was amplified for KRAS exon 1 and TP53exon 5-8 mutations by PCR-direct sequencing. Results Histopathologically, the tumors were classified into tubular(81.5%, 22/27), papillary (3.7%, 1/27), mucinous (3.7%, 1/27) and mixed types (11.1%, 3/27). Of the 27 CCAs,PCR-direct sequencing of KRAS showed G‡A transition at codon 37 exon 1 in one CCA sample (3.70%). Pointmutations of p53 exon 6 (G‡C transversion at codon 119 and 218 and A‡C transversion at codon 217) werefound in 3 CCA samples (11.1%).
Conclusions: The results suggest that mutation of TP53 particularly at exon 6may be involved in cholangiocarcinogenesis and a novel mutation of KRAS exon 1 was firstly reported in OVinducedhamster CCA.