"We were surprised to find such a strong correlation between CES and things like whether the patient survived five years later," said Karpen. "Another finding - one that is counterintuitive - is that high expression of these centromere genes is also related to more effective chemotherapy and radiation therapy."

The researchers hypothesized that the degree of chromosomal instability may also make cancer cells more vulnerable to the effects of chemotherapy or radiation therapy.


"In other words, there's a threshold of genome instability," said Zhang. "At low to medium-high levels, the cancer thrives. But at much higher levels, the cancer cells are more susceptible to the additional DNA damage caused by the treatment. This is a really key point."

The researchers pointed out that they found no link between very high levels of genome instability and improved patient survival without adjuvant treatments.

Translating these findings into clinical advice and practice will take more research, the study authors caution. They are working to find that threshold of genome instability so that in the future, doctors and patients can make informed decisions about how to move forward.

"Future steps will include investigating the CES in prospective clinical studies for validation in carefully selected patient cohorts," said Jain. "By establishing the clinical significance of the CES, oncologists will have greater confidence in guiding cancer patients toward treatments with the greatest benefit."

###

Other co-authors of the study are Jian-Hua Mao at Berkeley Lab's Division of Biological Systems and Engineering; Wei Zhu at the Cellular Biomedicine Group in Shanghai; and Ke Liu and James Brown at Berkeley Lab's Division of Environmental Genomics and Systems Biology. Mao and Zhu provided critical expertise in bioinformatics for this research.

The National Institutes of Health supported this work.

Lawrence Berkeley National Laboratory addresses the world's most urgent scientific challenges by advancing sustainable energy, protecting human health, creating new materials, and revealing the origin and fate of the universe. Founded in 1931, Berkeley Lab's scientific expertise has been recognized with 13 Nobel prizes. The University of California manages Berkeley Lab for the U.S. Department of Energy's Office of Science. For more, visit http://www.lbl.gov.

DOE's Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit science.energy.gov.

Back to HCB News

Medical Research Homepage