Cell-free DNA analysis for cancer diagnostics

Blood plasma contains numerous small fragments of DNA derived from cell types all over the body. In patients with cancer, a fraction of this cell-free DNA originates from tumor cells, and carries genomic features of the tumor. These include single base mutations, structural variants, and methylation markers. In addition, differences in enzymatic degradation create fragmentation signatures unique to patients with cancer. Circulating tumor DNA can help address multiple diagnostic needs for patients with cancer including early detection, monitoring of response to therapy and tracking disease evolution. Here are some review papers from our lab describing recent progress:
- The role of liquid biopsies in patients with breast cancer
- Biology of circulating DNA in health and disease
- Circulating tumor DNA analysis and opportunities for personalized cancer medicine
- Circulating tumor DNA as an early detection tool
Ultra-sensitive tumor DNA detection for minimal residual disease
Accurate detection of residual tumor cells after surgical or chemotherapeutic intervention has the potential to alter patient treatment plans, both to improve survival outcomes and reduce unnecessary treatments. Due to the very small amount of tumor-derived cfDNA in these patients, these diagnostic tests require extremely high sensitivity. We are developing personalized, multi-mutation approaches to identify tumor-specific mutations and detect these mutations in patient plasma during and after treatment. See some examples of our recent work below:
- Our most recent SVEN assay for tumor-guided structural variant detection (AACR 2024 abstract)
- The TARDIS assay for SNV detection and monitoring response to neoadjuvant therapy in patients with breast cancer
- Monitoring response to immunotherapy in patients with renal cell carcinoma

Cell-free DNA fragmentation analysis for cancer detection and treatment monitoring

DNA fragmentation differences inherent to tumor-derived cfDNA provide the opportunity to develop assays that require very little cfDNA and inexpensive sequencing. Leveraging this opportunity, our lab has developed a highly sensitive assay to distinguish patients with cancer from healthy individuals based on inferred differences in nucleosome positions. We are applying this approach to address multiple clinical challenges, including the stratification of patients with a high risk of pancreatic cancer. See some examples of our work below:
- Analysis of fragmentation patterns in urine cell-free DNA
- Genome-wide Analysis of Fragment Ends (the GALYFRE assay) for multi-cancer detection using plasma DNA whole genome sequencing
- Multianalyte blood-based risk stratification of incidental pancreas lesions
Development of cancer diagnostic assays for global health applications
Millions of people around the world lack access to the complex infrastructure required to deploy most cancer diagnostic approaches. Our lab has a strong interest in developing non-invasive diagnostics that are both affordable and logistically feasible in a variety of healthcare systems. Development in this area includes the design of diagnostic assays that require fewer resources and overcoming practical challenges such as sample collection, storage, and shipment. Some recent examples of our work:

Cancer diagnostics for veterinary oncology

Dogs have a significantly higher rate of cancer than humans, and some cancer types that are rare and difficult to study in humans are among the most common cancers in dogs. This presents both challenges in veterinary care and opportunities to study cancers that are rare in humans. Our lab is developing a range of molecular and diagnostic tools to enable the study of cancer-derived cfDNA in dogs, with the goal of benefiting both canine and human cancer care. Some recent examples of our work:
- Feasibility of cancer detection in dogs using plasma DNA analysis
- A recent review paper we participated in describing liquid biopsy applications in veterinary precision oncology.