Defect detector: plugging holes in a breast cancer-gene screen.A European genetic test catches mutations that are missed by the sole test commercially available in the United States to screen the so-called breast cancer genes, a new study shows.
The genes, called BRCA BRCA
One of two genes (designated BRCA1 and BRCA2) that help repair damage to DNA, but when inherited in a defective state increase the risk of breast and ovarian cancer. 1 and BRCA2, normally encode proteins that suppress rampant cell growth. But when these genes are mutated, they can yield defective proteins that leave a person vulnerable to cancer. A woman harboring a mutation in BRCA1, for example, faces a lifetime risk of 50 to 80 percent of developing breast cancer. A mutation in either BRCA gene also confers an increased risk of ovarian cancer ovarian cancer
Malignant tumour of the ovaries. Risk factors include early age of first menstruation (before age 12), late onset of menopause (after age 52), absence of pregnancy, presence of specific genetic mutations, use of fertility drugs, and personal history of breast .
Women with a known BRCA mutation can be closely monitored and frequently screened for breast cancer, or they may even choose to have their breasts or ovaries Ovaries
The female sex organs that make eggs and female hormones.
Mentioned in: Choriocarcinoma
ovaries (ō´v surgically removed to prevent disease.
In the United States, Myriad Genetics of Salt Lake City holds exclusive rights for testing for mutations in the BRCA genes. However, this exclusivity isn't recognized in Canada or Europe. In recent years, European researchers have devised other BRCA tests and have reported BRCA mutations that the Myriad test doesn't detect.
In the new study, geneticist ge·net·i·cist
A specialist in genetics.
a specialist in genetics.
geneticist Mary-Claire King of the University of-Washington in Seattle and her colleagues identified 291 women with breast cancer, 6 women with ovarian cancer, and 3 men with breast cancer. Even though each had at least four relatives diagnosed with breast or ovarian cancer, the 300 participants tested negative for BRCA mutations by Myriad's commercial test.
Using a Dutch test kit, King's team analyzed each person's BRCA genes. The scientists identified a BRCA mutation in 12 percent of the participants. The work appears in the March 22 Journal of the American Medical Association JAMA: The Journal of the American Medical Association is an international peer-reviewed general medical journal, published 48 times per year by the American Medical Association. JAMA is the most widely circulated medical journal in the world. .
The two BRCA genes can harbor any of 1,000 or so different mutations, which alter the protein ultimately produced by the cell. Many of the mutations result from a change in DNA DNA: see nucleic acid.
or deoxyribonucleic acid
One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. at a single position.
Myriad maintains that its screening test catches 99 percent of known mutations, but it can miss a defect that appears in only one of a person's two copies of the gene. The alternative technique, called multiplex ligation-dependent probe amplification Multiplex ligation-dependent probe amplification (MLPA) is a variation of the polymerase chain reaction that permits multiple targets to be amplified with only a single primer pair. , catches such mutations, King says.
The commercial test wasn't designed to ferret out every mutation hidden in a gene, says Gregory C. Critchfield, a pathologist and the president of Myriad. While the more exhaustive screen found what he considers "rare mutations," Critchfield says that King's team has produced "an important paper ... that answers the [mutation] question for a subset of patients."
The Myriad test "is not sufficient," King concludes. "There are women who ... are negative in normal genetic testing Genetic Testing Definition
A genetic test examines the genetic information contained inside a person's cells, called DNA, to determine if that person has or will develop a certain disease or could pass a disease to his or her offspring. but who nonetheless carry cancer-causing mutations. They cannot be detected by methods used in this country. We need to have nonexclusive licensing for patents on genes."