Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D; community with critical information on the tools, technologies, and trends that drive the biotech industry.
Issue link: http://gen.epubxp.com/i/155541
Translational Medicine Cell Reprogramming Collectively, these fndings unveil a much more complex set of epigenetic perturbations characterizing the malignant state than previously thought. "A general dysregulation of DNA methylation occurs in cancer," Dr. Feinberg explains. These structural insights into genome-wide DNA methylation led to a key observation. "We found an enormous overlap in the regions that are altered in several Continued from page 45 types of cancer and in those that are changed during stem cell reprogramming, and both of them are very much related to regions where DNA methylation normally changes in a tissue-specifc manner," he says. This pointed the researchers toward the possibility that, epigenetically, cancer cells may acquire methylation patterns similar to the ones that are found in other tissue types. By using experimental and modeling approaches to integrate these fndings, Dr. Feinberg and his colleagues revealed that the defning epigenetic trait in cancer is not so much the nature of the DNA methylation changes, as their stochasticity. "There is some type of randomization of the methylation pattern, and as a result a tumor might be much better defned by its departure from the normal epigenetic pattern than by a switch to a different pattern," Evaluate & Explore LIFE SCIENCE AT PITTCON 2014 Neurons reprogrammed from fibroblasts: The green color labels beta-3 tubulin, which is a specific neuronal marker, and the red color labels synapsin, which is another neuronal marker for synaptic interactions. Sheng Ding, Ph.D., UC-San Francisco Dr. Feinberg says. This is reminiscent of the stochasticity that can be observed during normal development, where highly variable DNA methylation patterns are reported even in genetically identical animals. "We think that the same is true in cancer, and the opening of this stochasticity allows cancer cells to be selected and to gain a growth advantage at the expense of the host," he adds. Early-Stage Cells Pitcon is the leading conference and expositon for the latest advances in Life Science. Atending Pitcon March 2-6, 2014 Ch i ca go, I l l i n o i s www.pitcon.org gives you a unique opportunity to get a hands-on look at cutng-edge product innovatons from leading companies. Partcipate in the Technical Program to learn about industry trends and discover new applicatons and methodologies used in life science. Topics include the latest in genomics, proteomics, biotechnology, metabolomics, bioanalytcal, and more. For more informaton on technical sessions, exhibitors and short courses, visit www.pitcon.org. Follow Us for special announcements 46 | September 1, 2013 | GENengnews.com | Genetic Engineering & Biotechnology News "We found a variety of proteins that are selectively secreted by early-stage pancreatic lesions," says Kenneth S. Zaret, Ph.D., professor of cell and developmental biology at the University of Pennsylvania Perelman School of Medicine. The absence of good disease progression markers, frequent delays in detection, and the fve-year survival rate that approximates 6%, are major challenges for the management of pancreatic adenocarcinoma. To establish an experimental system that facilitates the identifcation of blood markers associated with disease progression, Dr. Zaret and his colleagues allowed pancreatic ductal adenocarcinoma cells to undergo reprogramming to the pluripotent state, and hypothesized that some cells would subsequently redifferentiate into adult pancreatic tissue and recapitulate early stages of cancer development. While cells derived from most of the initial tumor samples did not exhibit malignant genotypes, one cell line generated pancreatic intraepithelial neoplasia precursor cells that, in a mouse model, progressed to the invasive stage. "This approach enabled us to obtain a very rare cell line after scanning many tumors, and additional changes might have allowed these rare events to be identifed," Dr. Zaret says. Introducing early-stage human cancer cells into the mouse model could allow the longitudinal identifcation of markers that could predict progression to invasiveness. "In this case, the animal would serve as a surrogate for humans to determine blood markers," says Dr. Zaret. The in vitro culturing of early-stage cells provided the opportunity to perform proteomic analyses to identify secreted proteins that could serve as potential markers. "We wanted to determine which proteins are stably detected in the bloodstream of mice harboring human lesions that have progressed to the invasive stage," he says.