title: Profiling lung adenocarcinoma by liquid biopsy: can one size fit all?
abstract: BACKGROUND
  Cancer 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.
  
  
  METHODS
  Here we bioinformatically profile the mutational and copy number spectrum of The Cancer Genome Network's lung adenocarcinoma dataset to uncover recurrently mutated genomic loci.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  With 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.
authors.affiliation: OneTest Diagnostics, Cambridge Applied Research, Future Business Centre, Cambridge, UK.|St. Edmund Hall, University of Oxford, Queen's Lane, Oxford, UK.
authors.forename: Harry W
authors.initials: HW
authors.lastname: Clifford
authors.affiliation: NHS Greater Glasgow and Clyde, University of Glasgow, Glasgow, UK.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Cassidy
authors.affiliation: UNC School of Medicine, University of North Carolina, Chapel Hill, NC USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Vaughn
authors.affiliation: OneTest Diagnostics, Cambridge Applied Research, Future Business Centre, Cambridge, UK.|Peterhouse, University of Cambridge, Trumpington Street, Cambridge, UK.
authors.forename: Evaline S
authors.initials: ES
authors.lastname: Tsai
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Bianka
authors.initials: B
authors.lastname: Seres
authors.affiliation: 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.
authors.forename: Nirmesh
authors.initials: N
authors.lastname: Patel
authors.affiliation: Aberdeen Royal Infirmary, University of Aberdeen, Aberdeen, UK.
authors.forename: Hannah L
authors.initials: HL
authors.lastname: O'Neill
authors.affiliation: OneTest Diagnostics, Cambridge Applied Research, Future Business Centre, Cambridge, UK.
authors.forename: Emil
authors.initials: E
authors.lastname: Hewage
authors.affiliation: 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.
authors.forename: John W
authors.initials: JW
authors.lastname: Cassidy
keywords: Cancer genomics; Circulating tumour DNA; Liquid biopsy; Lung adenocarcinoma; Mutation; Oncogene; SNV; Tumour suppressor; ctDNA