Monthly Archives: March 2014

WEDNESDAY, March 26, 2014 (HealthDay News) -- Scientists say they've constructed an "atlas" that maps the ways human genes are turned on and off, offering potentially important new insights into health and disease.

The new atlas builds on the achievements of the Human Genome Project -- the mapping of all of the approximately 20,500 human genes, first completed in 2003. Speaking at the time of the Human Genome Project's publication, Francis Collins, director of the U.S. National Human Genome Research Institute, called it "a shop manual, with an incredibly detailed blueprint for building every human cell."

The new gene-activity map describes those networks that govern genes' activity in major cells and tissues in the human body, according to a team of 250 experts from more than 20 countries.

"Now, for the first time, we are able to pinpoint the regions of the genome that can be active in a disease and in normal activity, whether it's in a brain cell, the skin, in blood stem cells or in hair follicles," Winston Hide, an associate professor of bioinformatics and computational biology at Harvard School of Public Health, said in a Harvard news release.

"This is a major advance that will greatly increase our ability to understand the causes of disease across the body," added Hide, who was one of the authors of the main paper in the March 27 issue of Nature.

The findings from the three-year project -- called FANTOM5 -- are described in a series of papers published in Nature and 16 other journals. The project was led by the RIKEN Center for Life Science Technologies in Japan.

In their work, Hide and his colleagues mapped the activity of 224,000 switches that turn human genes on and off. The map includes switches -- which are regions of DNA that manage gene activity -- across a wide range of cell and tissue types.

"We now have the ability to narrow down the genes involved in particular diseases based on the tissue cell or organ in which they work," Hide said. "This new atlas points us to the exact locations to look for the key genetic variants that might map to a disease."

"The FANTOM5 project is a tremendous achievement. To use the analogy of an airplane, we have made a leap in understanding the function of all of the parts. And we have gone well beyond that, to understanding how they are connected and control the structures that enable flight," David Hume, director of The Roslin Institute at the University of Edinburgh, Scotland, and a lead researcher on the project, said in a university news release.

"The FANTOM5 project has identified new elements in the genome that are the targets of functional genetic variations in human populations, and also have obvious applications to other species," he added.

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New Gene 'Atlas' Maps Human DNA Activity

UT Southwestern Medical Center researchers are developing a new predictive tool that could help patients with breast cancer and certain lung cancers decide whether follow-up treatments are likely to help.

Dr. Jerry Shay, Vice Chairman and Professor of Cell Biology at UT Southwestern, led a three-year study on the effects of irradiation in a lung cancer-susceptible mouse model. When his team looked at gene expression changes in the mice, then applied them to humans with early stage cancer, the results revealed a breakdown of which patients have a high or low chance of survival.

The findings, published online in Clinical Cancer Research, offer insight into helping patients assess treatment risk. Radiation therapy and chemotherapy that can destroy tumors also can damage surrounding healthy tissue. So with an appropriate test, patients could avoid getting additional radiation or chemotherapy treatment they may not need, Dr. Shay said.

"This finding could be relevant to the many thousands of individuals affected by these cancers and could prevent unnecessary therapy," said Dr. Shay, Associate Director for Education and Training for the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. "We're trying to find better prognostic indicators of outcomes so that only patients who will benefit from additional therapy receive it."

Dr. Shay's study closely monitored lung cancer development in mice after irradiation. His group found some types of irradiation resulted in an increase in invasive, more malignant tumors. He examined the gene expression changes in mice well before some of them developed advanced cancers. The genes in the mouse that correlated with poor outcomes were then matched with human genes. When Dr. Shay's team compared the predictive signatures from the mice with more than 700 human cancer patient signatures, the overall survivability of the patients correlated with his predictive signature in the mice. Thus, the classifier that predicted invasive cancer in mice also predicted poor outcomes in humans.

His study looked at adenocarcinoma, a type of lung cancer in the air sacks that afflicts both smokers and non-smokers. The findings also predicted overall survival in patients with early-stage breast cancer and thus offer the same helpful information to breast cancer patients; however the genes were not predictive of another type of lung cancer, called squamous cell carcinoma. Other types of cancers have yet to be tested.

The American Cancer Society estimates the risk of developing lung cancer to be 1 in 13 for men and 1 in 16 for women, including both smokers and non-smokers. Lung cancer is the second most common cancer in both men and women, accounting for about 13 percent of all new cancers, and about 27 percent of cancer deaths. The American Cancer Society estimates more than 224,210 new cases of lung cancer and nearly 160,000 deaths from lung cancer will occur in 2014. Survival statistics vary depending on the stage of the cancer and when it is diagnosed.

Dr. Shay's research is paid for in part by a five-year grant from NASA, which helps fund cancer research due to cancer risks faced by astronauts during space missions. The findings could lead to more individualized care and pave the way to better, more science-based care and decision making, he said.

"Personalized medicine is coming," Dr. Shay said. "I think this is the future -- patients looking at their risks of cancer recurrence and deciding what to do next. We can better tailor the treatment to fit the individual. That's the goal."

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Gene may predict if further cancer treatments are needed