Cholangiocarcinoma is a fatal malignant neoplasm originating from biliary tracts and
constitutes about 5-10% of primary liver cancers, characterized by a poor prognosis. High
prevalence in southeast and eastern Asia has been observed. At present, the cellular and
molecular mechanisms leading to oncogenesis of cholangiocarcinoma remain unclear.
The RAS gene product has a key role in controlling cell growth and differentiation through
its intrinsic GTPase activity. Point mutations that activate the RAS protein and its
downstream cascade have been observed in human tumors. Both KRAS and BRAF are members of the
RAS-RAF-MEK-ERK-MAP kinase pathway which mediates cellular response to growth signals.
Somatic KRAS mutations are found at high rates in leukemia, colon cancer, pancreatic cancer
and lung cancer. Studies from European and Japanese groups have recently described that
activating KRAS/ BRAF mutations may play a role in the carcinogenesis of cholangiocarcinoma
of the biliary tracts, but our preliminary data demonstrated low frequency of KRAS and BRAF
mutation in the same tumor as well as the results from Thailand. In this study, the
investigators hypothesize copy number changes rather than genetic mutation of either KRAS or
BRAF genes may be the key findings of Taiwanese cases of the adenocarcinoma from the biliary