In addition, loss of Pten expression was shown in the tumor cells of ICCs in AKP mice by immunohistochemical staining (Figure S3A,B), suggesting that the remaining wild-type Pten allele was inactivated by some mechanism such as loss of heterozygosity, loss-of-function mutation, and hypermethylation of its promoter region. The gene discussed is PTEN; the disease is neoplasm.