and about 50 per cent of lung cancers, US researchers have discovered.
This apparently critical gene is the most important of only a few genes clearly associated
with sporadic, rather than hereditary, breast cancer, says Masaaki Hamaguchi of the Cold Spring
Harbor Laboratory in New York, who led the work. Sporadic disease accounts for more than 90
per cent of breast and other cancers.
“This is a completely new type of tumour-suppressor gene. We don’t have a real clue
what this gene is doing yet in the normal cell – we have just opened a door to a new field,” says
“The question is: how many cancers can be treated just by turning on this gene?” he says.
“We know that more than half of breast cancers have to turn it off, so I believe the number would
be high.” Hamaguchi thinks treatments based on switching on the gene, dubbed DBC2, could be
available in three or four years.
Hamaguchi’s team first compared the genetic make-up of breast cancer and normal cells.
They noticed frequent differences in one region on chromosome eight. “We checked it out in
detail and found a very small region is frequently deleted in the breast cancer cells. And we
went on to identify six genes in this region,” he says.
Of the six, two were uncharacterized. In one, DBC2, Hamaguchi’s team found frequent
differences between the healthy and cancerous cells. “At this point, we thought it might be very
interesting,” he says.
They found that only about 50 per cent of 19 breast cancer samples and 14 lung cancer
samples were expressing DBC2, compared with 100 per cent of healthy controls. And mutations
in DBC2 were more frequent in breast cancer cells than mutations in other tumour suppressor
genes previously linked to the disease. These show up in only up to about 30 per cent of cases
Further work confirmed that when breast cancer cells lacking DBC2 are forced to express
the protein, the growth of these cells is inhibited. Much more work is now needed to characterise
the normal role of the gene, says Hamaguchi.
“This is not like other genes. We knew this type of structure existed, because it is in the
database, but no gene like this has been studied,” he says. “Even forgetting about cancer and just
talking about biology, this is a very interesting gene.”
Hamaguchi and his colleagues have worked for many years on genes involved in breast
cancer. Co-researcher Mary-Claire King at the University of Washington, predicted the location
of the first gene linked to hereditary breast cancer, BRAC1, in 1990. But teams at the University
of Utah, Myriad Genetics in Salt Lake City and the US government’s National Institute of
Environmental Health Sciences in North Carolina were the first to isolate the gene. Mutations in
BRCA1 and BRCA2 account for only about five per cent of breast cancers.
Breast cancer is the second leading cause of cancer death in women. About 40,000
women die from the disease every year in the US alone.