Comprehensive molecular profiling of extrahepatic cholangiocarcinoma in Chinese population and potential targets for clinical practice

Background:Cholangiocarcinoma(CCA)is a diverse group of malignancies arising from the intra-or extrahepatic biliary epithelium and characterized by its late diagnosis and fatal outcome.Extrahepatic cholangiocarcinoma(ECC)accounts for 90%of CCA.However,little is known about the comprehensive genomic alterations of ECC in Chinese population for providing clinical managements especially targeted therapy.Methods:Comprehensive genomic profiling(CGP)was performed with next generation sequencing panel on paraffin-embedded tumor from a cohort of 80 Chinese ECC patients.Results:The most frequently altered genes were TP53(68%),KRAS(46%),SMAD4(22%),ARID1A(20%)and CDKN2A(19%).Mutual exclusivity was observed between multiple genes including ARID1A:TP53,KRAS:LRP1B and NF2:TP53.Genetic alterations with potential therapeutic implications were identified in 43%of patients.The top three actionable alterations include CDKN2A(n=11),BRAF(n=5)and ERBB2(n=4).Potentially actionable alterations were mainly enriched in the G1-S transition,homologous recombination repair,MAPK/ERK pathway.Conclusions:This is the largest data set of ECC cases providing a comprehensive view on genetic alterations in Chinese population which differs significantly from a US cohort,and indicates the potential clinical implications for targeted therapies.

Co_(2)(CO)_(8)-mediated Selective Reductions of Propargyl Alcohol Derivatives to Alkenes

In the presence of Co_(2)(CO)_(8) and additives,propargyl alcohol derivatives could be reduced to alkenes in moderate to good yield.The selectivity of this reaction could be controlled by adding different additives:with H_(2)O as the additive,the major configuration of product is Z-alkene;with CF_(3)COOH as the additive,the major configuration of product is E-alkene.