Cancer May Have Stem Cell Origin

According to the study's findings, which are to be published in the February 2007 issue of the journal Nature Genetics and are now available online, genes that are reversibly suppressed in embryonic stem cells are over-represented among genes that are permanently silenced in tumors; this connection lends validation to the increasingly discussed hypothesis that cancer is rooted in small populations of stem cells.

University of Southern California (USC; Los Angeles, USA) researchers discovered this link after observing that of 177 genes repressed by Polycomb group (PcG) proteins, fully 77 demonstrated 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,” stated 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 at USC.

The investigators found that some genes repressed by Polycomb in embryonic stem cells are essentially pre-marked to become permanently silenced by DNA methylation. "This permanent silencing,” remarked Dr. Laird, "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 Dr. 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 added, "which points to epigenetic events preceding genetic events in cancer development.” Dr. Laird observed that this hypothesis, while comparatively new, is gathering 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; San Francisco, CA, USA), which was created through passage of California Proposition 71 in 2004. "One of CIRM's aims,” said Dr. 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.”

Dr. Laird and his USC colleagues would like to focus next on what causes some genes to transition from temporary repression to permanent silencing. "Once we determine that,” Dr. Laird explained, "we can turn to the fundamental question: How can we prevent this transition?”

Dr. Laird collaborated with colleagues at USC and the University College London (UK).



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