Mutations of KRAS and TP53 in a minor proportion of Opisthorchis viverrini-associated cholangiocarcinomas in a hamster model.

ABSTRACT

BACKGROUND/AIMS: KRAS oncogene and TP53 tumor suppressor gene have been known as common genes involving in many cancers including cholangiocarcinoma (CCC). Activation of these genes could lead to uncontrolled proliferation and cancer ultimately. The aim of this study was to investigate mutation of KRAS exon 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 N-nitrosodimethylnitrosamine (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 TP53 exon 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[see text]A transition at codon 37 exon 1 in one CCA sample (3.70%). Point mutations of p53 exon 6 (G[see text]C transversion at codon 119 and 218 and A[see text]C transversion at codon 217) were found in 3 CCA samples (11.1%). CONCLUSIONS: The results suggest that mutation of TP53 particularly at exon 6 may be involved in cholangiocarcinogenesis and a novel mutation of KRAS exon 1 was firstly reported in OV-induced hamster CCA.