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USC study in Nature Genetics supports a stem cell origin of cancer
January 10, 2007Researchers at the University of Southern California (USC) recently made significant strides toward settling a decades-old debate centering on the role played by stem cells in cancer development. According to the study's findings, which appear in an upcoming issue of Nature Genetics and now available online, genes that are reversibly repressed in embryonic stem cells are over-represented among genes that are permanently silenced in cancers; this link lends support to the increasingly discussed theory that cancer is rooted in small populations of stem cells.
USC researchers uncovered this link after observing that of 177 genes repressed by Polycomb group (PcG) proteins, fully 77 showed evidence of cancer-associated enzymatic modification of DNA (known as methylation). "Finding that a Polycomb target in an embryonic stem cell is 12 times more likely to become abnormally methylated in cancer is highly significant," says Peter Laird, Ph.D., one of the lead researchers and associate professor of surgery, biochemistry and molecular biology, and director of basic research for surgery at the Keck School of Medicine of USC.
Laird and his colleagues discovered that some genes repressed by Polycomb in embryonic stem cells are essentially pre-marked to become permanently silenced by DNA methylation. "This permanent silencing," Laird explains, "prevents embryonic stem cells from differentiating, and they thus become the seeds of cancer development later in life." USC researchers made these observations in relation to breast, colorectal, lung, and ovarian cancer.
Not only does the USC study provide empirical evidence for a stem cell origin of cancer, but, according to Laird, "It also supports a very early involvement of epigenetics in cancer. We found that cancer arises in cells that have already undergone epigenetic alterations," he adds, "which points to epigenetic events preceding genetic events in cancer development." Laird notes that this theory, while relatively new, is gaining support among scientists.
Findings from the USC study also can be applied to stem cell research funded by the California Institute for Regenerative Medicine (CIRM), which was created through passage of California Proposition 71 in 2004. "One of CIRM's aims," says Laird, "is to culture and differentiate embryonic stems cells - cells that would then be placed into patients. Since our research shows that cancer is rooted in stem cells, it would be very important to screen for the epigenetic abnormalities that we uncovered, so as to prevent people from receiving potentially cancer-prone cells."
Looking ahead, Laird and his USC colleagues would next like to focus on what causes some genes to transition from temporary repression to permanent silencing. "Once we determine that," Laird explains, "we can turn to the fundamental question: How can we prevent this transition?"
University of Southern California
Not only does the USC study provide empirical evidence for a stem cell origin of cancer, but, according to Laird, "It also supports a very early involvement of epigenetics in cancer. We found that cancer arises in cells that have already undergone epigenetic alterations," he adds, "which points to epigenetic events preceding genetic events in cancer development." Laird notes that this theory, while relatively new, is gaining support among scientists.
Findings from the USC study also can be applied to stem cell research funded by the California Institute for Regenerative Medicine (CIRM), which was created through passage of California Proposition 71 in 2004. "One of CIRM's aims," says Laird, "is to culture and differentiate embryonic stems cells - cells that would then be placed into patients. Since our research shows that cancer is rooted in stem cells, it would be very important to screen for the epigenetic abnormalities that we uncovered, so as to prevent people from receiving potentially cancer-prone cells."
Looking ahead, Laird and his USC colleagues would next like to focus on what causes some genes to transition from temporary repression to permanent silencing. "Once we determine that," Laird explains, "we can turn to the fundamental question: How can we prevent this transition?"
University of Southern California
Stem Cell Current Events and Stem Cell News RSSNew discovery about the formation of new brain cells
The generation of new nerve cells in the brain is regulated by a peptide known as C3a, which directly affects the stem cells' maturation into nerve cells and is also important for the migration of new nerve cells through the brain tissue, reveals new research from the Sahlgrenska Academy published in the journal Stem Cells.
Gene mismatch influences success of bone marrow transplants
A commonly inherited gene deletion can increase the likelihood of immune complications following bone marrow transplantation, an international team of researchers reports in the November 22 advance online issue of Nature Genetics.
New research shows versatility of amniotic fluid stem cells
For the first time, scientists have demonstrated that stem cells found in amniotic fluid meet an important test of potential to become specialized cell types, which suggests they may be useful for treating a wider array of diseases and conditions than scientists originally thought.
First reconstitution of an epidermis from human embryonic stem cells
Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
Your Own Stem Cells Can Treat Heart Disease
The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells.
U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence
A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning.
Researchers find potential treatment for Huntington's disease
Investigators at Burnham Institute for Medical Research (Burnham), the University of British Columbia's Centre for Molecular Medicine and Therapeutics and the University of California, San Diego have found that normal synaptic activity in nerve cells (the electrical activity in the brain that allows nerve cells to communicate with one another) protects the brain from the misfolded proteins associated with Huntington's disease.
Researchers 'notch' a victory toward new kind of cancer drug
Scientists have devised an innovative way to disarm a key protein considered to be "undruggable," meaning that all previous efforts to develop a drug against it have failed.
UCI embryonic stem cell therapy restores walking ability in rats with neck injuries
The first human embryonic stem cell treatment approved by the FDA for human testing has been shown to restore limb function in rats with neck spinal cord injuries - a finding that could expand the clinical trial to include people with cervical damage.
First use of antibody and stem cell transplantation to successfully treat advanced leukemia
For the first time, researchers at Fred Hutchinson Cancer Research Center have reported the use of a radiolabeled antibody to deliver targeted doses of radiation, followed by a stem cell transplant, to successfully treat a group of leukemia and pre-leukemia patients for whom there previously had been no other curative treatment options.
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