Just Say No to ATOH: How HIC1 Methylation Might Predispose Medulloblastoma to Lineage Addiction

Hypermethylated in cancer-1 (HICI) is a tumor suppressor frequently targeted for promoter hypermethylation in medulloblastoma, an embryonal tumor of the cerebellum. Recently, we showed that HICI is a direct transcriptional repressor of ATOH1, a proneural transcription factor required for normal cerebellar development, as well as for medulloblastoma cell viability. Because demethylating agents can induce reexpression of silenced tumor suppressors, restoring HICI function may present an attractive therapeutic avenue in medulloblastoma by exploiting an apparent addiction to ATOH1. [Cancer Res 2008;68(21):8654-6]