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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Unbiased Detection of Somatic Copy Number Aberrations in cfDNA of Lung Cancer Cases and High-Risk Controls with Low Coverage Whole Genome Sequencing.
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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