Plasma Whole-genome Sequencing to Detect and Characterize Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is the most prevalent and aggressive type of the pancreatic cancer, and is associated with extremely low survival rate. There are almost no symptoms in the early stage of this disease, so patients are usually diagnosed in the late stage where tumours have metastasized to other organs. Therefore, we are in an urgent need to develop an effective strategy to either detect onset of the cancer earlier in individuals with high risks of developing PDA, or detect recurrence/progression of the cancer earlier in already diagnosed patients. After cells die, they will release DNA into blood circulation, and this DNA will be in a form of free-floating small fragments, termed as cell-free DNA (cfDNA). The DNA fragments released from tumour cells are called circulating tumour DNA (ctDNA). ctDNA contains mutational information of the tumour, which gives us an opportunity to detect tumour with minimal invasion by extracting blood plasma and sequencing its cfDNA. Whole-genome sequencing (WGS) profiles the DNA sequences in the entire genome, so it is highly sensitive to detect ctDNA from plasma.

In this project, we aim to test whether plasma WGS can provide sensitive detection and accurate characterization of PDA. We have previously collected a cohort of plasma WGS data from PDA patients. First, we will develop an informatic tool to process this complex dataset to obtain robust results. Then, we will conduct further analyses by combining patients’ clinical data to understand how we can apply plasma WGS to monitor disease progression at the clinic. Finally, after we have in-depth understandings of this novel technology, we will extend its application to PDA early screening in high-risk individuals by developing computational models to detect early signs of tumour signals from plasma. Overall, this project will establish a plasma-based platform for sensitive PDA detection, hence early reactions can be conducted to maximize patients’ survival.

Quotes

“Pancreatic cancer is one of the most lethal malignancies. Patients are usually diagnosed at late stages and the disease can progress extremely fast. My project focuses on building a sensitive liquid biopsy platform to detect tumor signals from patients' blood plasma, so that this disease can be identified earlier and monitored effectively. I am really excited to receive the support from MOHCCN, as this will open to me great opportunities for dataset access, communication and collaboration with other researchers in the community.”

• Yuanchang Fang, HI&DS Awardee
  

“Plasma whole genome sequencing is emerging as a highly sensitive methodology for cancer detection from blood. In pancreatic cancer, even in advanced patients, circulating tumour DNA levels can be low and difficult to detect. Results so far in this deadly disease have been inconsistent with respect to detecting circulating tumour DNA. Yuanchang’s project will critically develop the methodologies to consistently detect circulating tumour DNA in pancreatic cancer using this highly sensitive technology. In the future, the goal is to apply in the setting of early detection.”

• Dr. Faiyaz Notta, mentor