Genome-wide analysis of aberrant position and sequence of plasma DNA fragment ends in patients with cancer
Budhraja et al. Science Translational Medicine 2023
Building on work first developed in the urine cfDNA publication, we leveraged publicly available data and our own samples to develop a cancer diagnostic test based on differential cfDNA fragmentation patterns in healthy individuals versus patients with cancer. We demonstrated that the aberrantly fragmented DNA is likely derived from the cancer cells themselves and is identifiable across a wide range of cancer types and stages.
Analysis of recurrently protected genomic regions in cell-free DNA found in urine
Markus et al. Science Translational Medicine 2021
Cell-free DNA found in urine presents an opportunity to develop diagnostics using an extremely easy to collect biofluid, but the basic features of urine cfDNA are poorly understood. In this study we conducted an extensive characterization of urine cfDNA, including its fragmentation profile, fragment end sequence motifs, and dominant cellular sources. We applied this information in a proof of principle analysis using samples from pediatric patients.
Personalized circulating tumor DNA analysis to detect residual disease after neoadjuvant therapy in breast cancer
McDonald et al. Science Translational Medicine 2019
Although many patients with early-stage cancers of several types, including breast cancer and colorectal cancer, are in remission after pre-operative chemotherapy and surgery, these patients still receive post-surgery chemotherapy in case there is residual tumor. Identifying the patients who do not require post-surgery chemotherapy would significantly improve the quality of life of these patients and reduce their medical costs. In this study we developed a personalized, highly sensitive assay to detect residual disease in early-stage breast cancer patients. We demonstrated detection of tumor DNA at 30 parts per million from a single tube of blood, and were able to distinguish patients with residual disease from those with pathological complete response.
Selected Publications
- Marcinak et al. Multianalyte blood-based risk stratification of incidental pancreas lesions. medRxiv [pre-print] 2024
- Chehrazi-Raffle et al. Ultrasensitive Circulating Tumor DNA Pilot Study Distinguishes Complete Response and Partial Response With Immunotherapy in Patients With Metastatic Renal Cell Carcinoma. JCO Precision Oncology 2023
- Marcinak et al. Characterization of copy number alterations in Pakistani patients with colorectal cancer. medRxiv [pre-print] 2023
- Favaro et al. Feasibility of circulating tumor DNA analysis in dogs with naturally occurring malignant and benign splenic lesions. Scientific Reports 2022
- Kisat et al. Plasma metagenomic sequencing to detect and quantify bacterial DNA in ICU patients suspected of sepsis: A proof-of-principle study. Journal of Trauma and Acute Care Surgery 2021
- Greytak et al. Harmonizing cell-free DNA collection and processing practices through evidence-based guidance. Clinical Cancer Research 2020
- Markus et al. Evaluation of pre-analytical factors affecting plasma DNA analysis. Scientific Reports 2018
- Murtaza et al. Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer. Nature Communications 2015
- Murtaza et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 2013
- Dawson et al. Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer. NEJM 2013
- Forshew et al. Noninvasive Identification and Monitoring of Cancer Mutations by Targeted Deep Sequencing of Plasma DNA. Science Translational Medicine 2012