Abstract
Molecular profiling using low coverage whole genome sequencing of cell free DNA (cfDNA) represents a non-targeted approach to identify multiple somatic copy number alterations (SCNA) across different lung cancer subtypes. We aim to establish that SCNA can be detected in cfDNA of lung cancer cases.
Standard protocols were followed to process matched cfDNA, formalin-fixed paraffin embedded (FFPE) tumour and lymphocyte DNA. Copy number profiles for cfDNA or FFPE DNA were normalised to profiles from matched lymphocyte DNA with the software CNAnorm. Technical sensitivity was determined by spiking different proportions of FFPE tumour DNA into cfDNA from controls.
The median genome coverage was 0.26X (range 0.05X–0.97X). For two advanced stage cases there was a positive correlation between copy number ratio profiles of matched cfDNA and FFPE DNA (r = 0.62, p < 0.0001 and r = 0.75, p < 0.0001). There was no correlation for four advanced and two early stage cases. There were low magnitude copy number aberrations detected in high-risk controls (N = 5). We detected spiked FFPE DNA derived SCNAs with a tumour fraction as low as 10 % of cfDNA.
Our preliminary results demonstrate non-invasive detection of tumour-derived copy number alterations in advanced lung cancer cases with low coverage whole genome sequencing. Clinical characteristics and treatment may influence whether SCNA are detected in cfDNA.
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Acknowledgements
We would like to thank Yorkshire Cancer Research and Cancer Research UK for supporting this PhD project, Weston Park Hospital Cancer Charity for funding ResoLuCENT and The British Association of Cancer Research for providing travel funds. Prof. Jacqui Shaw from the University of Leicester and Dr. Henry Wood from the University of Leeds are thanked for their technical support.
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© 2016 Springer International Publishing Switzerland
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Taylor, F., Bradford, J., Woll, P.J., Teare, D., Cox, A. (2016). Unbiased Detection of Somatic Copy Number Aberrations in cfDNA of Lung Cancer Cases and High-Risk Controls with Low Coverage Whole Genome Sequencing. In: Gahan, P., Fleischhacker, M., Schmidt, B. (eds) Circulating Nucleic Acids in Serum and Plasma – CNAPS IX. Advances in Experimental Medicine and Biology, vol 924. Springer, Cham. https://doi.org/10.1007/978-3-319-42044-8_6
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DOI: https://doi.org/10.1007/978-3-319-42044-8_6
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