The gene hypermethylated in cancer-1 (HIC1) encodes a zinc-finger transcription factor1 that belongs to a group of proteins known as the POZ family2. HIC1 is hypermethylated and transcriptionally silent in several types of human cancer1,3-5. Homozygous disruption of Hic1 impairs development and results in embryonic and perinatal lethality in mice6. Here we show that mice disrupted in the germ line for only one allele of Hic1 develop many different spontaneous malignant tumors, including a predominance of epithelial cancers in males and lymphomas and sarcomas in females. The complete loss of Hic1 function in the heterozygous mice seems to involve dense methylation of the promoter of the remaining wild-type allele. We conclude that HIC1 is a candidate tumor-suppressor gene for which loss of function in both mouse and human cancers is associated only with epigenetic modifications.
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