Among the mutations that may affect the epigenetic regulation, we observed one BAP1 missense mutation as well as additional missense mutations on MLL3 (KMT2C), SETD2, SETDB1, and TSHZ2 suggesting that the histone modification may be largely perturbed by somatic mutations during ICC development. The gene discussed is TSHZ2; the disease is intrahepatic cholangiocarcinoma.