This type of methylation produces an abnormal off switch that in this case inappropriately shuts down production of a tumor suppressor protein, said Markowitz. The methylation process has also been implicated in turning off other tumor suppressor genes and is recognized as a contributor to the development of cancer.

When the scientists introduced a functional copy of the HLTF gene into the colon cancer cell lines that lacked the gene, the cells stopped growing. This finding suggests that the HLTF gene is itself a tumor suppressor gene that can stop tumors from growing.

Markowitz said that the studies also hint that drugs that reverse methylation may be a new type of cancer treatment. These drugs are now in the early stages of development. In the short term, however, Markowitz believes the finding may help doctors diagnose colon cancer and perhaps differentiate aggressive, invasive tumors from less aggressive forms of colon cancer.

When Markowitz and his colleagues looked in lung and breast cancer cells, they found the HLTF gene was normal. Based on this result, they concluded that the HLTF gene may be involved specifically in colon cancer progression. Furthermore, the scientists had previously detected abnormal methylated DNA in the blood of some colon cancer patients, suggesting that if the findings hold for the commonly methylated HLTF gene, it could be a target for a new diagnostic test for colon cancer. Markowitz cautioned that the result needs to be duplicated and other cancer cells need to be tested.

Markowitz is optimistic, and he cites recent work by HHMI investigator Bert Vogelstein at The Johns Hopkins University School of Medicine that demonstrates a new targeted, non-invasive test for finding about half of colon cancers using the APC tumor sup
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
2-Apr-2002