胆道肿瘤基础研究进展与展望

The basic research progress and prospect on biliary tract cancer

胆管癌是一种来源于肝内或肝外胆管上皮的恶性肿瘤,是最具挑战和备受关注的胆道疾病.其发生的主要诱因尚无法明确,大多数学者认为是通过长期的表观遗传学改变的累积,从而导致原癌基因和肿瘤抑制因子异常,进而诱导胆管癌的发生发展.最近的研究表明一系列涉及细胞周期调控、细胞信号通路以及核染色体动力学高复发的基因突变可能在胆管癌发生中起到关键性的作用.本文主要介绍胆管癌中潜在关键基因改变与功能,以及在胆管癌的发生、发展中的作用及展望.

Objective Cholangiocarcinoma （CCA） is a malignant tumour of bile duct epithelial cells with dismal prognosis and rising incidence.Recent research show that the major contributing factor of cholangiocarcinogenesis is likely through accumulation of serial genetic and epigenetic alterations resulting in aberration of oncogenes and tumour suppressors.Recent studies making use of advances in high-throughput genomics have revealed the genetic landscape of CCA, greatly increasing our understanding of its underlying biology.A series of highly recurrent mutations in genes which are known to be involved in cell cycle control, cell signaling pathways and chromatin dynamics, have led to investigations of their roles, through molecular to mouse modelling studies, in cholangiocarcinogenesis.This review focuses on the landscape genetic alterations in CCA and its functional relevance to the formation and progression of CCA, their roles in the development and progression of cholangiocarcinoma.