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Archive - Mar 29, 2012

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Egg Protein Found Critical to Epigenetic Stability

An international team led by scientists at A*STAR’s Institute of Medical Biology (IMB) has discovered that a protein, called TRIM28, normally present in the mother’s egg, is essential right after fertilization to preserve certain chemical modifications or “epigenetic marks” on a specific set of genes. The study, published in the March 23, 2012 issue of Science, paves the way for more research to explore the role that epigenetics might play in infertility. Previous studies have shown that both nuclear reprogramming as well as “imprinting” are vital for the survival and later development of the embryo. However, the underlying mechanisms governing the intricate interplay of these two processes during the early embryonic phase have not been clear, until now. Immediately after fertilization, the majority of the epigenetic marks on the DNA from the sperm and egg cells are erased. The erasure process, termed nuclear reprogramming, allows the genes from the parents to be reset so that the early embryonic cells can develop into any cell types of the body. On the other hand, certain epigenetic marks on a particular set of genes, some from the mother and some from the father must be preserved. These genes are said to be “imprinted” by their parent of origin and preservation of these marks is critical for the survival of the newly formed embryo. Expression of these imprinted genes at the appropriate levels ensures proper development of the embryo. If the epigenetic marks on the imprinted genes are not protected, severe and multiple developmental defects occur in the embryo. Using genetically identical mice from an inbred mouse strain, Drs. Davor Solter and Barbara Knowles, Senior Principal Investigators at IMB, observed that none of the embryos resulting from the fertilization of eggs lacking TRIM28 survived.

New Breast Cancer Susceptibility Gene Identified Using Exome Sequencing

Rare mutations in a gene called XRCC2 cause increased breast cancer risk, according to a study published online on March 29, 2012 in the American Journal of Human Genetics. The study looked at families that have a history of the disease, but do not have mutations in the currently known breast cancer susceptibility genes. Sean Tavtigian, Ph.D., a Huntsman Cancer Institute (HCI) investigator and associate professor in the Department of Oncological Sciences at the University of Utah (U of U) is one of three co-principal investigators on the study, along with David Goldgar, Ph.D., professor in the Department of Dermatology at the U of U and an HCI investigator, and Melissa Southey, Ph.D., professor in the Department of Pathology at the University of Melbourne, Australia. "We have added to the list of genes that harbor mutations causing breast cancer," said Dr. Tavtigian. "This knowledge will improve breast cancer diagnostics and add years to patients' lives. More important, relatives who have not been affected by the disease, but carry the mutations, will benefit even more. They can find out they are at risk before they have cancer and take action to reduce their risk or catch the cancer early." XRCC2 may also provide a new target for chemotherapy. "A type of drug called a PARP inhibitor appears to kill tumor cells that have gene mutations in a particular DNA repair pathway. XRCC2 is in this pathway, as are BRCA1 and BRCA2. It's reasonably likely that a breast cancer patient who has a mutation in XRCC2 will respond well to treatment with PARP inhibitors," said Dr. Tavtigian. According to Dr. Tavtigian, many breast cancer cases appear in families with a weak history of the disease.