Journal article

Identification of mutations in circulating cell-free tumour DNA as a biomarker in hepatocellular carcinoma

Jessica Howell, Stephen R Atkinson, David J Pinato, Susanne Knapp, Caroline Ward, Rosalba Minisini, Michela E Burlone, Monica Leutner, Mario Pirisi, Reinhard Buettner, Shahid A Khan, Mark Thursz, Margarete Odenthal, Rohini Sharma

European Journal of Cancer | ELSEVIER SCI LTD | Published : 2019

Abstract

BACKGROUND: Hepatocellular carcinoma (HCC) is increasing globally. Prognostic biomarkers are urgently needed to guide treatment and reduce mortality. Tumour-derived circulating cell-free DNA (ctDNA) is a novel, minimally invasive means of determining genetic alterations in cancer. We evaluate the accuracy of ctDNA as a biomarker in HCC. METHODS: Plasma cell-free DNA, matched germline DNA and HCC tissue DNA were isolated from patients with HCC (n = 51) and liver cirrhosis (n = 10). Targeted, multiplex polymerase chain reaction ultra-deep sequencing was performed using a liver cancer-specific primer panel for genes ARID1A, ARID2, AXIN1, ATM, CTNNB1, HNF1A and TP53. Concordance of mutations in ..

View full abstract

Grants

Awarded by Starter Grant Scheme of the Academy of Medical Sciences (AMS) (Academy of Medical Sciences)


Awarded by Starter Grant Scheme of the Academy of Medical Sciences (AMS) (Wellcome Trust)


Awarded by Starter Grant Scheme of the Academy of Medical Sciences (AMS) (Medical Research Council)


Awarded by Starter Grant Scheme of the Academy of Medical Sciences (AMS) (British Heart Foundation)


Awarded by Starter Grant Scheme of the Academy of Medical Sciences (AMS) (Arthritis Research UK)


Awarded by Starter Grant Scheme of the Academy of Medical Sciences (AMS) (Royal College of Physicians)


Awarded by Starter Grant Scheme of the Academy of Medical Sciences (AMS) (Diabetes UK)


Funding Acknowledgements

The authors greatly appreciate the technical assistance of Ulrike Koitzsch in NGS library construction, and they thank Hannah Eischeid for her technical assistance in DNA extraction. Furthermore, they are very grateful for the support of QIAgen Inc for providing the reagents for extraction of circulating DNA and the Human Liver Cancer GeneRead DNAseq targeted panel V2.The authors gratefully acknowledge the support of the R&D funding of Medical Faculty of the University Cologne (Germany) and the Center of Molecular Medicine Cologne, as well as the UK National Institute for Health Research grant, which provides support for the Imperial Biomedical Research Centre.Dr Jessica Howell is supported by an NHMRC Sidney Sax Postdoctoral Fellowship.Dr David Pinato is supported by National Institute for Health Research (NIHR), grant funding from the Imperial NIHR Biomedical Research Centre (BRC) and Starter Grant Scheme of the Academy of Medical Sciences (AMS, Grant ID SGL013/1021; supported by the Academy of Medical Sciences, The Wellcome Trust, Medical Research Council, British Heart Foundation, Arthritis Research UK, the Royal College of Physicians and Diabetes UK).