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Published: Saturday, 4/17/2004

Researcher uses grant of $1M to examine gene involved in colon cancer

BY JENNI LAIDMAN
BLADE SCIENCE WRITER

A Medical College of Ohio researcher is using a $1 million, five-year grant from the National Cancer Institute to find out why some genes always get it wrong.

Kandace J. Williams, a molecular biologist, is studying "one of the key events in cancer progression," said Douglas L. Pittman, another researcher at the college.

Dr. Williams concentrates on a couple of mistake-prone hot spots on genes associated with one variety of cancer known as hereditary nonpolyposis colon cancer. In the hot spot, a mere three errors occur in the 6,000 nucleotides that make the gene. Nucleotides are the chemical "letters" of DNA.

"We're looking at one of the hottest hot spots," Dr. Williams said. This gene is mutant in nearly half of all human tumors.

Normally, repair genes put such errors right - like a good spell-check program. But in cancers, the repair genes consistently miss these errors, or fix them incorrectly.

When mistakes linger in certain genes, the result can be a continuous command to the cell to grow and divide, in other words, cancer.

"It's like a light switch that doesn't work anymore,'' Dr. Williams said.

To learn more about these repair hot spots, Dr. Williams makes a little circle of genetic material that carries a gene with a mistake in the hot spot. Then she sees what the cells' repair proteins do to this flawed specimen. She wants to see whether proteins mend the gene perfectly, make a mess of the fix-it project, or leave the bad gene alone.

"Most people would argue there's a lack of repair,'' said Lawrence Loeb, a researcher at the University of Washington School of Medicine in Seattle. Dr. Williams "is invoking the idea that ... this is error-prone repair.''

She hypothesizes that the genetic spell checker simply fails at the so-called hot spots - as though this portion of the genome contained words the spell checker mistakenly treats as correct.

Ultimately, Dr. Williams hopes to learn what makes the hot spots so hot, and why the repair process fails.

"Our belief is once you truly understand what causes cancer, then you can start thinking about a way to effectively battle it,'' Dr. Williams said.


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