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. 2015 Feb;98(1):106-12.
doi: 10.1016/j.yexmp.2014.12.009. Epub 2015 Jan 3.

Development and validation of the JAX Cancer Treatment Profile™ for detection of clinically actionable mutations in solid tumors

Guruprasad Ananda  1 , Susan Mockus  1 , Micaela Lundquist  1 , Vanessa Spotlow  1 , Al Simons  2 , Talia Mitchell  1 , Grace Stafford  2 , Vivek Philip  2 , Timothy Stearns  2 , Anuj Srivastava  2 , Mary Barter  2 , Lucy Rowe  2 , Joan Malcolm  1 , Carol Bult  2 , Radha Krishna Murthy Karuturi  1 , Karen Rasmussen  1 , Douglas Hinerfeld  3
Affiliations

Development and validation of the JAX Cancer Treatment Profile™ for detection of clinically actionable mutations in solid tumors

Guruprasad Ananda et al. Exp Mol Pathol. 2015 Feb.

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.

Keywords: Actionable; Cancer; FFPE; Mutation; Panel.

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Figures

Figure 1
Figure 1
JAX-CTP™ workflow from sample receipt through clinical report generation.
Figure 2
Figure 2
Depiction of a complex indel (a heterozygous deletion of AGGGGG and insertion of CTTCACACACA) in PMS2 gene from a colon adenocarcinoma patient sample: (A) Pile up of reads at the locus: Deletion represented by a solid pink horizontal line and Insertion by a solid orange vertical line. (B) UCSC Genome Browser track showing the two alleles at this locus.
Figure 3
Figure 3
Comparison of copy-number profiles from JAX-CTP™ with NanoString for a squamous cell carcinoma patient sample. Red and blue crosses represent exon (or probe) level log ratios measured by JAX-CTP™ and NanoString respectively. Red and blue lines represent the averages of the exon (or probe) level log ratios measured by JAX-CTP™ and NanoString respectively.
Figure 4
Figure 4
Each bar represents the number of genes (Y axis) of the JAX-CTP™ within each of the described biological pathways (X axis).
See this image and copyright information in PMC

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