Target molecular treatment markers in Intrahepatic Cholangiocarcinoma based on Chinese population

Abstract

Background: As more and more molecular markers have been identified in Intrahepatic Cholangiocarcinoma (ICC), target treatments are promising all around the world. However, geographical and ethnic variations in the ICC epidemiology suggest different genetic variance prevalence in western and eastern countries.

Methods: Six genetic variations in Chinese ICC populations were analyzed by fluorescent in situ hybridization (FISH) or Sanger sequencing, listed as IDH1/2 mutation, FGFR2 translocation, NTRK1 amplification, MDM2 amplification, HER2 amplification and MET amplification, all of which have corresponding target drugs; meanwhile, they were compared with these gene prevalence in Spanish population based on the cBioPortal database.

Results: The incidences of IDH1/2 mutation, FGFR2 translocation, NTRK1 amplification, MDM2 amplification, HER2 amplification and MET amplification were 29.5 %, 12.9 %, 1.51 %, 2.27 %, 3.03 % and 0.75 %, respectively, in the Spanish population and 7.14 %, 5.71 %, 7.86 %, 5.71 %,4.29 % and 2.14 %, respectively, in the Chinese population. For the gene NTRK1, 11 samples showed signal apart companied amplified using FISH break-apart probes but none of them demonstrated genetic fusion by next-generation sequencing. As to clinicopathological characteristics, patients carrying IDH1/2 mutation showed longer overall survival in the Chinese population, while those carrying FGFR2 translocation tended to be younger in the Spanish population. For HER2, MDM2 and MET, gene amplification predicted protein high-expression, whereas FGFR2 translocation and NTRK1 amplification did not predict protein high-expression.

Conclusions: Although many target drugs have been speeded up for approval such as BGJ398 for FGFR2 fusion positive ICC patients in western countries, the beneficiary populations are very small in China. The regular target drug such as trastuzumab for HER2 amplification and Crizotinib for MET amplification may be potential candidates in target treatment based on the Chinese population.

Keywords: FGFR2; HER2; IDH1/2; Intrahepatic Cholangiocarcinoma; MDM2; MET; NTRK1.