AMHERST, Mass. – An epidemiologist and two experts in highly targeted, next-generation gene sequencing studies at the University of Massachusetts Amherst have teamed up on research to validate a potential new method for early identification of breast cancer-related changes. The work could help to identify women at higher risk and lead to new prevention strategies.
Epidemiologist Susan Sturgeon of the School of Public Health and Health Sciences (SPHHS) at UMass Amherst recently received the two-year, $760,462 National Cancer Institute award to use data and blood samples from the Prostate, Lung, Colorectal, Ovarian (PLCO) Screening Trial to validate a methylation profile that could help to distinguish whether white blood cell (WBC) DNA methylation change might predict the future likelihood of breast cancer.
She leads a team that includes environmental toxicologist Kathleen Arcaro of the veterinary and animal sciences department, genomic biologist David Sela of the food science department and biostatistician Raji Balasubramanian of SPHHS.
Arcaro says the team approach is notable. “I think the award demonstrates the value of collaborative research at UMass Amherst. Working together as a team, we can enhance the epidemiologic work and bring a new dimension to cancer research. This sort of cooperation represents the most promising way forward in investigating new prevention and risk assessment strategies for breast cancer.”
In cancer research, methylation, in which Arcaro is an expert, is a relatively new and important area. Methylation occurs in the DNA at so-called CpG sites (cytosine-phosphate-guanine), which are associated with promotion or suppression of gene expression. One particularly promising topic is the possibility of monitoring the methylation status of some genes as a biomarker for the presence of tumorigenesis, or tumor growth.
Sturgeon says, “This study has the potential to reduce mortality by leading to the development of a risk assessment tool for breast cancer. Characterization of a WBC DNA breast cancer-related risk profile could help in better targeting of risk-reduction strategies of high risk women and could lead to the development of novel prevention strategies.”
The National Institutes of Environmental Health (NIEHS) Sister Study recently identified a panel of five differently methylated CpGs between breast cancer cases and control subjects using prospectively collected white blood cell WBC DNA and a genomic array of 27,578 CpG sites.
As the researchers explain, “We will further extend the findings of the Sister Study by capitalizing on serial bloods available in PLCO to robustly investigate the association in two different time intervals between WBC DNA collection and diagnosis.” The time periods are from one to two, and four to seven years.
“This analysis will provide the information necessary to distinguish whether WBC DNA methylation changes are a response to preclinical breast cancer and further clarify the lead time, and/or if they predict the future likelihood of breast cancer.”
Arcaro adds, “We’ll use targeted, next-generation sequencing of bisulfite-modified DNA for the present validation study of the top five CpGs, due to the method’s high accuracy, sensitivity and precision. BiSulfite Amplicon Sequencing (BSAS) combines the benefits of bisulfite conversion and tagmentation-based library construction with the digital quantitation provided by next-generation sequencing.”