Clinical validation of the tempus xT next-generation targeted oncology sequencing assay

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Accurate detection of somatic alterations and microsatellite instability (MSI) is crucial for cancer diagnosis and treatment.
• Existing methods may require substantial tissue samples, limiting their use in certain clinical scenarios.

Purpose of the Study:

• To develop and clinically validate a hybrid capture next-generation sequencing (NGS) assay for comprehensive genomic profiling in solid tumors and hematologic malignancies.
• To assess the assay's performance in detecting various genomic alterations, including single nucleotide variants, indels, gene rearrangements, copy number variations, and MSI.

Main Methods:

• Utilized a hybrid capture NGS approach with tumor-normal matched samples.
• Incorporated whole transcriptome RNA sequencing for unbiased gene fusion detection.
• Validated the assay using a combination of clinical specimens and cell lines.

Main Results:

• Achieved high sensitivity across all tested metrics: 99.1% for single nucleotide variants, 98.1% for indels, 99.9% for gene rearrangements, 98.4% for copy number variations, and 99.9% for MSI detection.
• Demonstrated the assay's ability to conserve limited tissue samples while providing a wide array of clinically relevant data.

Conclusions:

• The developed hybrid capture NGS assay is a clinically validated, sensitive, and comprehensive tool for detecting somatic alterations and MSI in various cancer types.
• This assay supports informed clinical management decisions and facilitates patient enrollment in clinical trials by efficiently utilizing limited tissue resources.