Poster Presentation 29th Lorne Cancer Conference 2017

Systematic approach to methylation biomarker development in chronic lymphocytic leukemia, breast and lung cancers (#288)

Tomasz K Wojdacz 1 2 , Johanne A Windeløv 2 , Britta B Thestrup 2 , Tine E Damsgaard 3 , Dianna Dominguez 2 , Tina Kjeldsen 2 , Lasse S Kristensen 2 , Henrik Hager 4 , Jens Overgaard 5 , Lise Lotte Hansen 2
  1. Aarhus Institute of Advanced Studies , University of Aarhus, Aarhus C, Denmark
  2. Department of Biomedicine, University of Aarhus , Aarhus C
  3. Department of Plastic Surgery,, University of Aarhus , Aarhus C, Denmark
  4. Department of Pathology, Aarhus University Hospital , Aarhus C, Denmark
  5. Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus C, Denmark

There is no doubt that testing for disease specific methylation changes can guide disease risk assessment, facilitate detection of the disease, support prognostication and personalization of treatment as well as guide post treatment patient care (1).

Nevertheless, the use of methylation biomarkers in standard patient care is still marginal. Difficulties in implementation of methylation biomarker testing in standard in-vitro diagnostics are mainly attributed to challenges in establishment of the systematic approach allowing for efficient discovery and subsequent validation of clinical utility of potential disease specific methylation biomarkers.

We have combined state of the art genome wide methylation screening technologies (including: newest Illumina MethylationEPIC 850k BeadChip) enabling methylation biomarker discovery with the cost and time efficient locus specific technologies to streamline the development, validation and implementation of methylation biomarkers in clinical disease management.

With the use of technologies that in affordable fashion enable screening genome wide methylation changes in substantial number of clinical samples we were able to discover clinically relevant patient and disease specific methylation signatures e.g. in CLL. The high technical complexity the genome wide screen technologies still makes them not straightforward applicable in diagnostic settings. Thus we used techniques such as Methylation Sensitive High Resolution Melting (2) to develop assays fulfilling requirements for diagnostic applications and subsequently using those assays we evaluated clinical relevance of the most promising biomarker candidates in chronic lymphocytic leukaemia, breast and lung cancers (3, 4).

Overall our workflow allows fast and efficient validation of not only already existing biomarker candidates but also discovery of new disease specific methylation changes that show promise for clinical implementation.

 

(1) Wojdacz TK. Expert Rev Mol Diagn. 2012 Jan;12(1):39-47

(2) for BLUEPRINT consortium, Nature Biotechnology, Vol. 34, Nr. 7, s. 726-737.

(3) Daugaard I et al, Sci Rep. 2016 Oct 26;6:35807.

(4) Wojdacz TK et at. Breast Cancer Res. 2014 Feb 3;16(1):R17