Hypermethylated Genes Involved in Cancer Development

Cancer researchers have found that loss of the hypermethylated-in-cancer 1 gene (Hic1), which encodes a zinc-finger transcription factor but fails to function in several types of human cancer, induces gender-linked development of cancers in a mouse model. Their findings were published in the February 2003 issue of Nature Genetics.

Investigators from Johns Hopkins University's Kimmel Cancer Center (Baltimore, MD, USA; www.jhu.edu) genetically engineered a line of mice that lacked one copy of the Hic1 gene. Mice completely lacking the gene failed to develop past the embryo stage.

When the modified mice were more than 70 weeks old, excessive cancers begin to emerge. By 90 weeks of age, 16.4% of the experimental mice had developed tumors, while no normal mice had. By 100 weeks, experimental mice had almost three times the rate of tumors as normal mice (34.2 % versus 14.3% of normal mice). The kind of tumors that appeared depended on the mouse's sex. Female mice tended to develop lymphomas and sarcomas, while male mice developed more epithelial cancers.

"Most genes linked to cancer were first identified from mutations in families, and subsequently some of the same genes were found to be hypermethylated, but Hic1 was identified solely because of extra methylation in cancer cells,” explained senior author Dr. Stephen Baylin, professor in the cancer biology division of John Hopkins University. "Now we have shown directly that loss of the gene's function leads to cancers in mice.”

Whether the gender effects seen in mice are present in human cancers remains to be learned.



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