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Researchers identify gene set linked to breast cancer's spread to lungs
Researchers identify gene set linked to breast cancer's spread
to lungs
July 28, 2005
In a potential advance for the treatment of aggressive breast
cancer, scientists at Memorial Sloan-Kettering Cancer Center
(MSKCC) have identified a set of genes in breast tumors that appear
to predict if the disease will spread to the lungs and, once there,
how virulent it will become.
The findings shed new light on the
biology of breast cancer metastasis, and could lead to a possible
prognostic tool and new targets for breast cancer treatment.
"Our work shows that the ability of a tumor to form metastases
depends on the combined action of multiple genes - and a different
set of genes is required for each
organ the tumor spreads to,"
said Joan Massagué, PhD, Chairman, Cancer Biology and Genetics
Program, at MSKCC, who led the study. "Based on these insights,
we can now seek genes for metastasis by other tumors and to
other organs," added Massagué, who is also a Howard Hughes
Medical Institute investigator. The findings appear in the July
28, 2005 issue of Nature.
In a 2003 study, Dr. Massagué and his colleagues identified a
gene pattern in breast cancer cells that are prone to spread to
bone. The latest work shows that the genes that prompt breast
tumors to spread to the lungs are almost entirely different from
the earlier set, with only six genes in common. This finding is
surprising as it had been previously assumed that genes that
dictate metastases to specific organs did not exist.
To uncover genes involved in breast cancer metastasis, Dr.
Massagué's group used a cell line from a breast cancer patient
treated for aggressive tumors that had spread to many other organs.
From this line they identified cancer cells that showed a
propensity for migrating to the lungs but not the bone when
transplanted into mice.
Using a microarray - or "gene chip" - the researchers were able
to analyze the cells to see how their genetic activity differed
from that of breast cancer cells that did not show a proclivity for
lung metastases in the rodents.
Some genes function more vigorously
than usual while the activity of others was suppressed.
The gene "thumbprint" was then verified in a group of 82 early
stage breast tumors removed from patients at MSKCC. More than half
(55 percent) of patients whose primary tumors showed the genetic
"thumbprint" went on to develop lung metastases, compared with only
10 percent of those whose primary tumors did not carry the gene
set.
"Metastasis, particularly to visceral organs such as the lung,
accounts for the majority of breast cancer related mortality," said
Andy J.
Minn, MD, PhD, a radiation oncologist at MSKCC, and first
author of the
Nature paper. The new research
"may provide genetic markers to aid oncologists in clinical
management, offer potential therapeutic targets to develop drugs
against metastasis, and give basic researchers a paradigm to
understand how metastatic ability is acquired," Dr. Minn
said.
As the gene thumbprint is narrowed to as small a set as
possible, researchers could develop diagnostic tests that
incorporate this genetic information, Dr.
Massagué noted. The
research team is also looking for similar patterns of gene activity
in other cancers with a proclivity to spread to the lungs.
Dr. Massagué added that there are drugs already on the market
that target a few of the genes discovered in the new study.
"If you
can successfully target these genes with a drug, you are helping
slow the growth of any primary tumor and also blocking the growth
of any tumor cells that have spread to the lungs," he said.
The next step for the researchers is a study involving a larger
number of breast cancers, including those from patients at other
medical centers. They are also searching for gene patterns in other
forms of cancer that often spread to the lungs.
Memorial Sloan-Kettering Cancer Center
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