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Development and validation of the JAX Cancer Treatment Profile™ for detection of clinically actionable mutations in
Guruprasad Ananda1, Susan Mockus1, Micaela Lundquist1
1The Jackson Laboratory for Genomic Medicine, 10 Discovery Dr., Farmington, CT 06032, USA.
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.
Insights
The JAX Cancer Treatment Profile™ (JAX-CTP™) is a validated next-generation sequencing assay for detecting actionable mutations and amplifications in solid tumors. This molecular profiling supports targeted cancer therapy selection.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genomics
Background:
- Advancements in targeted cancer therapeutics necessitate sophisticated tumor molecular profiling methods.
- The JAX Cancer Treatment Profile™ (JAX-CTP™) is a novel next-generation sequencing (NGS)-based assay designed for this purpose.
Purpose of the Study:
- To validate the JAX-CTP™ assay for detecting actionable mutations in solid tumors.
- To establish the assay's utility in guiding the selection of targeted cancer treatments.
Main Methods:
- DNA extracted from formalin-fixed paraffin-embedded tumors is used for NGS library generation.
- Hybrid capture enriches target genes, followed by sequencing on Illumina platforms.
- Variant detection, functional, and clinical annotation are performed to generate a comprehensive report.
Main Results:
- The JAX-CTP™ assay detects actionable single nucleotide variations and small insertions/deletions (≤50 bp) in 190 genes.
- The assay requires a minimum neoplastic cell content of 10% and is validated for detecting clinically actionable gene amplifications.
Conclusions:
- Communicating validation methods for NGS assays in oncology is crucial due to a lack of consensus.
- Refined tumor profiling assays are essential for precision cancer treatment, driven by increasing targeted therapies and genomic complexity.