RESEARCH
CANCER AND AGING / SOMATIC MUTATIONS / EARLY CANCER DETECTION
Research at the Risques Lab focuses on the study of somatic mutations in aging and early cancer with the ultimate goal of enabling the development of better biomarkers for early cancer detection and prediction. Currently, our main projects involve the application of ultra-accurate deep sequencing to characterize somatic mutations; to detect cancer mutations in liquid biopsies, and to determine how cancer risk factors shape the clonal landscapes of human tissues.
STUDY OF AGE-RELATED SOMATIC MUTATIONS AND THEIR ASSOCIATION WITH CANCER RISK
Cancers evolve through mutation, selection, and clonal expansion. While mutations in human tumors have been extensively characterized, little is known about how mutations accumulate as we age and how they contribute to cancer formation. Using ultra-accurate sequencing, we discovered that cancer-likeTP53 mutations occur at very low level in individuals with and without cancer, and they increase with age. This indicates the action of somatic evolution through life and suggests that the measurement of these mutations might be an indication of future cancer risk. We are currently working on proving this hypothesis.
DETECTION OF CANCER MUTATIONS IN LIQUID BIOPSIES
Our lab pioneered the use of Duplex Sequencing, an ultra-accurate next-generation sequencing method, to detect very low frequency mutations for early cancer detection. Specifically, we used Duplex Sequencing to detect high-grade serous ovarian cancer in peritoneal fluid and uterine lavage via ultra-accurate TP53 deep sequencing. We are currently expanding these initial studies with the ultimate goal of developing early cancer detection biomarkers for ovarian cancer, especially for the population of women at high risk.
INVESTIGATE HOW CANCER RISK FACTORS SHAPE THE CLONAL LANDSCAPES OF NORMAL TISSUES
The interplay of mutation and selection in our normal tissues results in the creation of complex clonal landscapes. Mutant clones differ by tissue type and often, but not always, are driven by the same mutations that drive cancers. Most importantly, we and others have demonstrated that clonal landscapes are shaped by cancer risk factors. For example, the normal bladder tissue of males and smokers is enriched for specific types of mutant clones. We are currently investigating the clonal landscapes of human tissues and how they are influenced by cancer risk factors.