title: Comparative mutational landscape analysis of patient-derived tumour xenografts.
abstract: BACKGROUND
  Screening of patients for cancer-driving mutations is now used for cancer prognosis, remission scoring and treatment selection. Although recently emerged targeted next-generation sequencing-based approaches offer promising diagnostic capabilities, there are still limitations. There is a pressing clinical need for a well-validated, rapid, cost-effective mutation profiling system in patient specimens. Given their speed and cost-effectiveness, quantitative PCR mutation detection techniques are well suited for the clinical environment. The qBiomarker mutation PCR array has high sensitivity and shorter turnaround times compared with other methods. However, a direct comparison with existing viable alternatives are required to assess its true potential and limitations.
  
  
  METHODS
  In this study, we evaluated a panel of 117 patient-derived tumour xenografts by the qBiomarker array and compared with other methods for mutation detection, including Ion AmpliSeq sequencing, whole-exome sequencing and droplet digital PCR.
  
  
  RESULTS
  Our broad analysis demonstrates that the qBiomarker's performance is on par with that of other labour-intensive and expensive methods of cancer mutation detection of frequently altered cancer-associated genes, and provides a foundation for supporting its consideration as an option for molecular diagnostics.
  
  
  CONCLUSIONS
  This large-scale direct comparison and validation of currently available mutation detection approaches is extremely relevant for the current scenario of precision medicine and will lead to informed choice of screening methodologies, especially in lower budget conditions or time frame limitations.
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Brait
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Izumchenko
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Luciane T
authors.initials: LT
authors.lastname: Kagohara
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Long
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Piotr T
authors.initials: PT
authors.lastname: Wysocki
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Faherty
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Elana J
authors.initials: EJ
authors.lastname: Fertig
authors.affiliation: Champions Oncology, Baltimore, MD 21205, USA.
authors.forename: Tin Oo
authors.initials: TO
authors.lastname: Khor
authors.affiliation: Champions Oncology, Baltimore, MD 21205, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bruckheimer
authors.affiliation: Champions Oncology, Baltimore, MD 21205, USA.
authors.forename: Gilson
authors.initials: G
authors.lastname: Baia
authors.affiliation: Champions Oncology, Baltimore, MD 21205, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ciznadija
authors.affiliation: Champions Oncology, Baltimore, MD 21205, USA.
authors.forename: Ido
authors.initials: I
authors.lastname: Sloma
authors.affiliation: Champions Oncology, Baltimore, MD 21205, USA.
authors.forename: Ido
authors.initials: I
authors.lastname: Ben-Zvi
authors.affiliation: Champions Oncology, Baltimore, MD 21205, USA.
authors.forename: Keren
authors.initials: K
authors.lastname: Paz
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.|Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
mesh_terms: D000818:Animals; D004252:DNA Mutational Analysis / Q000379:methods*; D064593:Heterografts / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D015203:Reproducibility of Results; D014407:Tumor Cells, Cultured