Course The Biology and characteristic of circulating cell free DNA and circulating tumour DNA in health and disease

Title: The Biology and characteristic of circulating cell free DNA and circulating tumour DNA in health and disease

Reg.no: C304/01

is being offered by the Graduate School of Health, Aarhus University, spring 2021

Criteria for participation: University degree in medicine, dentistry, nursing, or Master’s degree in other fields and/or postgraduate research fellows (PhD students and research-year medical students).

The participant must write a short application to be accepted for attendance at the course. This application shall state why the applicant wishes to attend, the level of background knowledge, and the purpose of taking the course. The size of the application is limited to 2500 characters (including spaces).  The purpose of the application is to enable prioritization of motivated applicants with urgent needs for the course.

Your application must be sent to Course administrator (annette@au.dk) before 22 March 2021

Aim: To qualify the students to conduct circulating tumour DNA (ctDNA) based research projects

Learning outcomes:

1. Basic knowledge of cell free DNA biology and markers of ctDNA.
2. The necessary knowledge needed to avoid, or at least control for, biases introduced by pre-analytical processing.
3. Basic understanding of the pros and cons of present state-of-the-art methods and technologies used to analyse cell free DNA (cfDNA) and ctDNA. To enable the student to choose the method/technology best suited in a given situation.
4. Knowledge about the clinical situations where ctDNA may potentially be used to guide clinical decision making
5. Knowledge about pros and cons of different cfDNA/ctDNA trial designs.
6. To qualify the student to design and conduct their own cfDNA/ctDNA study

Content: Modules:

The biology of cell free and circulating tumor DNA: This module will provide the audience with a fundamental understanding of the biology of cell free and circulating tumor DNA and how working with these opens new possibilities in research and the clinic. The lectures will cover: The cellular origin of the cell free DNA circulating in plasma of healthy and diseased individuals (Somatic mosaism, Chronic/acute diseases, Cancer, Age), mechanisms of how DNA is released to the circulation, circulating cell free DNA and tumor DNA during the course of disease and strengths and weakness of markers of cfDNA and ctDNA, including: Methylation, Mutations, Copy number variations, Fragmentation patterns, Fragment size, Mitochondrial DNA copies, Microbiome DNA

Critical pre-analytical factors: The lectures will focus on relevant pre-analytical considerations for designing a clinical study. Issues regarding blood collection and processing of cfDNA will be addressed including the best time to draw blood, which vials to use, how to process and store samples, and how to purify cfDNA. The lectures will also cover QC strategies and measures.

Detection methods and interpretation of cfDNA and ctDNA measurements: This module will cover the detection and quantification of cfDNA/ctDNA with focus on both tumor and non-tumor informed approaches. The lectures will focus on: PCR based approaches for detecting circulating cell free/tumor DNA, next Generation sequencing approaches e.g. multiplex PCR NGS, ultra-deep targeted sequencing, shallow whole genome sequencing, tumor-informed whole genome sequencing processing and QC controls, bioinformatics analysis of ctDNA measurements, interpretation of ctDNA results in clinical context (tumor and non-tumor informed) and multimarker and multianalyte strategies

Potential clinical application and implementation. These lectures will cover all the ctDNA research center clinical focus areas: Early cancer detection, guiding adjuvant therapy decisions, risk stratified postoperative recurrence surveillance, monitoring ctDNA levels to predict therapy response, and identification of therapeutically actionable targets.

The lectures will focus on: Areas where ctDNA guided clinical decision making have potential to change clinical practice, Clinical trial design considerations, Examples of Danish and International trials exploring the clinical benefit of ctDNA guided clinical decision making. Considerations regarding clinical implementation, including cost/benefit and health economics

The course participants must present the designs and underlying considerations of the studies/trials they are preparing or working on.

Language: English

Instructors: Claus Lindbjerg Andersen, Mai-Britt Worm Ørntoft, Sarah Østrup Jensen, Lars Dyrskjøt, Rikke Fredslund Andersen, Karen-Lise Garm Spindler, Kåre Gotschalck Sunesen, Niels Pallisgaard m.fl

Time and date: 19 - 20 May 2021

Venue: Online teaching

Course fee: DKK 1680.

Participation in the course is without cost for:

• PhD students, Research Year students and Research Honours Programme students from Aarhus University
• PhD students enrolled at partner universities of the Nordoc collaboration
• PhD students from other institutions in the open market agreement for PhD courses

Course dates:

• 19 May 2021 09:00 - 18:00
• 20 May 2021 09:00 - 15:30