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Minimizing Sample Failure Rates for Challenging Clinical Tumor Samples.

J Lynn Fink¹, Binny Jaradi², Nathan Stone²

¹XING Genomic Services, Sinnamon Park, Queensland, Australia; Australian Translational Genomics Centre, Queensland University of Technology, Woolloongabba, Queensland, Australia; The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, Queensland, Australia.

The Journal of Molecular Diagnostics : JMD

|February 11, 2023

Summary

This summary is machine-generated.

This study evaluated a new cancer sequencing technology (SLIMamp) on challenging samples. The technology successfully generated clinical reports for 77% of samples, identifying actionable cancer variants.

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Area of Science:

Genomics
Oncology
Molecular Diagnostics

Background:

Somatic variant identification via high-throughput sequencing is crucial for cancer targeted therapies.
High sample quality control (QC) failure rates can limit diagnostic test results.
Stem-loop inhibition mediated amplification (SLIMamp) technology is integrated into commercial cancer sequencing kits, claiming improved performance on difficult samples.

Purpose of the Study:

To validate the efficacy of SLIMamp technology in interrogating challenging formalin-fixed, paraffin-embedded (FFPE) cancer samples.
To assess the sample QC pass rate and the identification of clinically significant variants using the Pillar Biosciences oncoReveal Solid Tumor Panel.
To develop a novel post-sequencing QC metric for distinguishing reportable from unreportable samples.

Main Methods:

Acquisition of 48 FFPE samples with prior preanalytical QC failures for whole-exome sequencing.
Testing of samples using the Pillar Biosciences oncoReveal Solid Tumor Panel incorporating SLIMamp technology in an ISO15189-accredited laboratory.
Development and application of a novel post-sequencing QC metric.

Main Results:

Clinical reports were generated for 37 (77%) of the 48 tested samples.
Clinically actionable or significant variants were identified in 29 (60%) of the successfully reported samples.
Eleven (23%) samples were unreportable, with sequencing data likely affected by artifacts. A novel QC metric was developed to differentiate reportable from unreportable results.

Conclusions:

SLIMamp technology demonstrates potential for improving success rates in sequencing challenging FFPE cancer samples.
The technology can identify clinically relevant somatic variants in samples that might otherwise fail QC.
A new post-sequencing QC metric aids in reliable interpretation of sequencing data from difficult samples.