Cancer Gene Plot Thickens

Cancer clue. The new finding was triggered by chromosomes forming similar structures in both diseases.

A gene that causes a rare childhood leukemia is the same one that was fingered several years ago as a breast cancer gene, according to a study published online 13 June by Science. The finding points researchers to a particular cellular process that might run afoul in breast cancer, and it also suggests a slew of other genes that might make people vulnerable to various tumors.

About 20% of breast cancers are inherited, but the known susceptibility genes account for just a small portion of these breast tumors. Best known are the BRCA genes, which cells need to repair broken DNA. Because susceptibility genes can help predict cancer and unravel its course, researchers are constantly searching for new ones.

Now, they are getting help from an obscure disease called Fanconi anemia that runs in about 500 American families. The disease retards growth and causes bone defects in children and makes them susceptible to a variety of cancers. Fanconi is caused by any one of eight defects in human chromosomes, six of which had been pinpointed to proteins that flock together to help repair damaged DNA. The other two defects, called FA-B and FA-D1, had not been located.

While looking at breast cancer cells under the microscope, pediatrician Alan D'Andrea of the Dana-Farber Cancer Institute in Boston realized their chromosomes form distinct, abnormal structures, like spokes on a wheel, also seen in cells from Fanconi patients. "On kind of a whim," D'Andrea says he decided to test FA-B and FA-D1 cells for BRCA mutations. Sure enough, he found that short pieces were missing from both copies of the BRCA2 protein in each cell type. Further tests conclusively showed that the BRCA2 gene was mutated in both. D'Andrea thinks Fanconi may arise when both copies of any of the eight Fanconi or BRCA genes are mutated, while one damaged copy can make people vulnerable to breast and other cancers. Breast cancer researchers may benefit from what is known about Fanconi anemia, he says, because the same DNA repair proteins are involved in both conditions.

The work brings together completely distinct areas in DNA repair, says Alan Ashworth of the Institute of Cancer Research in London. Fanconi anemia and breast cancer are like "two facets of the same disease," he says, predicting that the search for cancer susceptibility genes will now turn to Fanconi anemia.

Related sites
Alan D'Andrea's Web site
Fanconi Anemia Research Fund Inc.

Follow News from Science