Profiling lung adenocarcinoma by liquid biopsy: can one size fit all?

Cancer Nanotechnology

Research

Hannah L. O’Neill¹  Bianka Seres²  Amy P. Cassidy³  Emil Hewage⁴  Nirmesh Patel⁵  Evaline S. Tsai⁶  John W. Cassidy⁷  Harry W. Clifford⁸  Courtney Vaughn⁹ 

[1] Aberdeen Royal Infirmary, University of Aberdeen, Aberdeen, UK;Max Planck Institute for Biophysical Chemistry, Göttingen, Germany;NHS Greater Glasgow and Clyde, University of Glasgow, Glasgow, UK;OneTest Diagnostics, Cambridge Applied Research, Future Business Centre, Cambridge, UK;OneTest Diagnostics, Cambridge Applied Research, Future Business Centre, Cambridge, UK;Division of Cancer Studies, King’s Health Partners AHSC, Faculty of Life Sciences and Medicine, King’s College London, London, UK;OneTest Diagnostics, Cambridge Applied Research, Future Business Centre, Cambridge, UK;Peterhouse, University of Cambridge, Trumpington Street, Cambridge, UK;OneTest Diagnostics, Cambridge Applied Research, Future Business Centre, Cambridge, UK;Queens’ College, University of Cambridge, Silver Street, Cambridge, UK;Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK;OneTest Diagnostics, Cambridge Applied Research, Future Business Centre, Cambridge, UK;St. Edmund Hall, University of Oxford, Queen’s Lane, Oxford, UK;UNC School of Medicine, University of North Carolina, Chapel Hill, NC, USA;

关键词: Lung adenocarcinoma;    Cancer genomics;    Mutation;    Tumour suppressor;    Oncogene;    SNV;    Circulating tumour DNA;    ctDNA;    Liquid biopsy;   

DOI  :  10.1186/s12645-016-0023-8

 received in 2016-06-28, accepted in 2016-11-08,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundCancer is first and foremost a disease of the genome. Specific genetic signatures within a tumour are prognostic of disease outcome, reflect subclonal architecture and intratumour heterogeneity, inform treatment choices and predict the emergence of resistance to targeted therapies. Minimally invasive liquid biopsies can give temporal resolution to a tumour’s genetic profile and allow the monitoring of treatment response through levels of circulating tumour DNA (ctDNA). However, the detection of ctDNA in repeated liquid biopsies is currently limited by economic and time constraints associated with targeted sequencing.MethodsHere we bioinformatically profile the mutational and copy number spectrum of The Cancer Genome Network’s lung adenocarcinoma dataset to uncover recurrently mutated genomic loci.ResultsWe build a panel of 400 hotspot mutations and show that the coverage extends to more than 80% of the dataset at a median depth of 8 mutations per patient. Additionally, we uncover several novel single-nucleotide variants present in more than 5% of patients, often in genes not commonly associated with lung adenocarcinoma.ConclusionWith further optimisation, this hotspot panel could allow molecular diagnostics laboratories to build curated primer banks for ‘off-the-shelf’ monitoring of ctDNA by droplet-based digital PCR or similar techniques, in a time- and cost-effective manner.

【 授权许可】

CC BY   
© The Author(s) 2016