title: Development and validation of the JAX Cancer Treatment Profile™ for detection of clinically actionable mutations in solid tumors.
abstract: BACKGROUND
  The continued development of targeted therapeutics for cancer treatment has required the concomitant development of more expansive methods for the molecular profiling of the patient's tumor. We describe the validation of the JAX Cancer Treatment Profile™ (JAX-CTP™), a next generation sequencing (NGS)-based molecular diagnostic assay that detects actionable mutations in solid tumors to inform the selection of targeted therapeutics for cancer treatment.
  
  
  METHODS
  NGS libraries are generated from DNA extracted from formalin fixed paraffin embedded tumors. Using hybrid capture, the genes of interest are enriched and sequenced on the Illumina HiSeq 2500 or MiSeq sequencers followed by variant detection and functional and clinical annotation for the generation of a clinical report.
  
  
  RESULTS
  The JAX-CTP™ detects actionable variants, in the form of single nucleotide variations and small insertions and deletions (≤50 bp) in 190 genes in specimens with a neoplastic cell content of ≥10%. The JAX-CTP™ is also validated for the detection of clinically actionable gene amplifications.
  
  
  CONCLUSIONS
  There is a lack of consensus in the molecular diagnostics field on the best method for the validation of NGS-based assays in oncology, thus the importance of communicating methods, as contained in this report. The growing number of targeted therapeutics and the complexity of the tumor genome necessitate continued development and refinement of advanced assays for tumor profiling to enable precision cancer treatment.
authors.affiliation: The Jackson Laboratory for Genomic Medicine, 10 Discovery Dr., Farmington, CT 06032, USA.
authors.forename: Guruprasad
authors.initials: G
authors.lastname: Ananda
authors.affiliation: The Jackson Laboratory for Genomic Medicine, 10 Discovery Dr., Farmington, CT 06032, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Mockus
authors.affiliation: The Jackson Laboratory for Genomic Medicine, 10 Discovery Dr., Farmington, CT 06032, USA.
authors.forename: Micaela
authors.initials: M
authors.lastname: Lundquist
authors.affiliation: The Jackson Laboratory for Genomic Medicine, 10 Discovery Dr., Farmington, CT 06032, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Spotlow
authors.affiliation: The Jackson Laboratory for Mammalian Genetics, 600 Main St, Bar Harbor, ME 04609, USA.
authors.forename: Al
authors.initials: A
authors.lastname: Simons
authors.affiliation: The Jackson Laboratory for Genomic Medicine, 10 Discovery Dr., Farmington, CT 06032, USA.
authors.forename: Talia
authors.initials: T
authors.lastname: Mitchell
authors.affiliation: The Jackson Laboratory for Mammalian Genetics, 600 Main St, Bar Harbor, ME 04609, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Stafford
authors.affiliation: The Jackson Laboratory for Mammalian Genetics, 600 Main St, Bar Harbor, ME 04609, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Philip
authors.affiliation: The Jackson Laboratory for Mammalian Genetics, 600 Main St, Bar Harbor, ME 04609, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Stearns
authors.affiliation: The Jackson Laboratory for Mammalian Genetics, 600 Main St, Bar Harbor, ME 04609, USA.
authors.forename: Anuj
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: The Jackson Laboratory for Mammalian Genetics, 600 Main St, Bar Harbor, ME 04609, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Barter
authors.affiliation: The Jackson Laboratory for Mammalian Genetics, 600 Main St, Bar Harbor, ME 04609, USA.
authors.forename: Lucy
authors.initials: L
authors.lastname: Rowe
authors.affiliation: The Jackson Laboratory for Genomic Medicine, 10 Discovery Dr., Farmington, CT 06032, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: Malcolm
authors.affiliation: The Jackson Laboratory for Mammalian Genetics, 600 Main St, Bar Harbor, ME 04609, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Bult
authors.affiliation: The Jackson Laboratory for Genomic Medicine, 10 Discovery Dr., Farmington, CT 06032, USA.
authors.forename: Radha Krishna Murthy
authors.initials: RK
authors.lastname: Karuturi
authors.affiliation: The Jackson Laboratory for Genomic Medicine, 10 Discovery Dr., Farmington, CT 06032, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Rasmussen
authors.affiliation: The Jackson Laboratory for Genomic Medicine, 10 Discovery Dr., Farmington, CT 06032, USA. Electronic address: Douglas.hinerfeld@jax.org.
authors.forename: Douglas
authors.initials: D
authors.lastname: Hinerfeld
mesh_terms: D000465:Algorithms; D019295:Computational Biology; D004273:DNA, Neoplasm / Q000032:analysis*; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D058977:Molecular Sequence Annotation; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D016612:Paraffin Embedding; D011379:Prognosis; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins
keywords: Actionable; Cancer; FFPE; Mutation; Panel