Combing through the DNA of nonhereditary breast cancers, scientists have found a gene that is mutated in 50% or more of breast and lung cancers. The gene codes for a protein that is unlike other cancer-causing proteins and may be the first member of a new gene family. The results will eventually help researchers understand how many breast and lung cancers arise.
Most of the genes known to cause breast cancer, such as the BRCA genes, have been found because they run in families with a high incidence of the disease. But inherited breast cancer accounts for less than 10% of the 200,000 breast cancer cases diagnosed annually in the United States. The other 90% or so arise when genes inside breast cells mutate in the course of a woman's life. But pinpointing these mutations has been hampered by the complexity of the disease.
To search for genes involved in sporadic breast cancer, researchers led by molecular biologist Masaaki Hamaguchi of Cold Spring Harbor Laboratory in New York compared DNA from cancerous and healthy cells from 200 women with breast cancer. The team noticed that in seven women, a gene called DBC2 had been completely deleted in cancerous cells. Reasoning that less drastic defects in DBC2 might be even more common, the team looked for the gene's messenger RNA (mRNA) in cells from 56 samples of breast, lung, and colon cancer and in cells from 19 healthy tissue samples. The mRNA showed up in all of the normal tissues but was missing in half of the lung cancers and 58% of the breast cancers. Inserting a normal DBC2 gene into cultured cancer cells stopped the cells' uncontrolled growth, they report online 7 October in the Proceedings of the National Academy of Sciences. The protein predicted by DBC2's DNA sequence has a region similar to a common cancer-causing gene, Hamaguchi says, but the rest is unusual. "DBC2 has a unique structure. We don't have a clue what this does normally."
The next step is to determine if mutant DBC2 causes breast cancer, and if so, how, says cancer geneticist Ramon Parsons at Columbia University in New York City. "DBC2 could be very important, but time will tell."