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Archive - Jun 10, 2009

Next-Gen Sequencing Reveals Single Genetic Change in Some Ovarian Cancers

Using powerful “next-generation” sequencing technology, researchers in Canada have sequenced the entire genome of a rare and often untreatable form of ovarian cancer (granulosa cell tumors) from four individuals and shown that the tumors share a single base change in the gene FOXL2. This gene encodes a transcription factor known to be critical for granulosa cell development. The research team further validated its work by examining a large number of additional tumor samples from across Canada and around the world, and the team is satisfied it has been able to validate that this mutation is present in almost all granulosa cell tumors and not in unrelated cancers. Most types of cancers, including most ovarian cancers, have a broad range of genetic abnormalities. The current finding shows that granulosa cell tumors have a characteristic single DNA spelling mistake that can serve as an easy-to-read identity tag for this cancer type. "This is really a two-fold discovery," said Dr. David Hunstman, senior author of the research report. "It clearly shows the power of the new generation of DNA sequencing technologies to impact clinical medicine, and for those of us in the area of ovarian cancer research and care, by identifying the singular mutation that causes granulosa cell tumours, we can now more easily identify them and develop news ways to treat them." For this effort, the research team used next-generation sequencing machines that are able to decode billions of nucleotides at rapid speed, together with new computer techniques to quickly assemble the data. "This task would have been unfathomable in terms of both cost and complexity even two years ago," said Dr. Marco Marra, also an author of the report. This work was published in the June 11 issue of the New England Journal of Medicine.

Four New Targets (LPA Pathway) for Breast Cancer Therapies

Researchers at the M.D. Anderson Cancer Center have identified four related new potential targets for breast cancer therapies. These potential targets are three lysophosphatidic acid (LPA) receptors (LPA1, LPA2, and LPA3) and the LPA-producing enzyme, autotoxin (ATX). "Lysophosphatidic acid is the single most potent known cellular survival factor," said senior author Dr. Gordon Mills. It binds to a series of G protein-coupled receptors to spark normal cell proliferation, viability, production of growth factors, and survival. The current research shows that this powerful network is hijacked to initiate breast cancer and fuel tumor growth, invasion, and metastasis. The authors show that breast cancer-resistant mice, when engineered to overexpress any one of the four molecules, develop invasive and metastatic mammary cancers. “We've compiled lots of evidence that they (LPA1, LPA2, LPA3, and ATX) are associated with cancer; what's been missing is proof that they could cause cancer. There are no questions left; they should be targeted." A number of drugs that target the receptors and ATX are currently in preclinical development, Dr. Mills said. "Now we have transgenic mouse models to test drugs to go forward against these targets." The current research was published in the June edition of Cancer Cell. [Press release] [Cancer Cell abstract]

Beetle Shell May Be Clue to Whiter, Lighter Paper

The brilliant white shell of an obscure beetle (Cyphochilus) has provided scientists with insights as to how to produce a brighter coating for white paper. The novel coating would also be thinner and lighter than current coatings and this would translate into reduced transportation costs, while simultaneously reducing the economic and environmental costs of manufacture. Cyphochilus is native to south-east Asia, and it is believed that its whiteness evolved to mimic local white fungi as a form of camouflage. In 2007, research conducted at the University of Exeter and Imerys Minerals Ltd., and published in Science, revealed how the beetle produces its brilliant whiteness using a unique surface structure of long, flat, ultrathin scales with highly random internal 3-D structures--ideal for creating whiteness, which results from the scattering of all colors simultaneously. In the new work, members of the same research team showed how some of the beetle’s shell structure can be mimicked to produce thinner, whiter coatings for white paper. "It is interesting to consider that clues found in a small, obscure beetle could find application in large-scale industry,” one of the researchers noted. “Taking this concept forward is an interesting challenge, but we have good ideas about our next steps and, if successful, feel that such developments might have profound implications for future commercial white coatings.” The current research was published in the June 10 issue of Applied Optics. [Press release] [Applied Optics abstract]