Illumina Inc. (NASDAQ: ILMN), a global leader in DNA sequencing and array-based technologies, today announced a new generation of its distributed liquid biopsy assay for genomic profiling. The new TruSight™ Oncology 500 ctDNA v2 (TSO 500 ctDNA v2) is a research assay that enables noninvasive comprehensive genomic profiling (CGP) of circulating tumor DNA (ctDNA) from blood when tissue testing is not available, or to complement tissue-based testing

Key improvements include a faster sample-to-answer turnaround time of less than four days, higher sensitivity with lower cell-free DNA (cfDNA) input requirements, and a more streamlined workflow, which will be further enabled with automation in the first half of 2024.

"Leading cancer centers are increasingly adopting the use of liquid-biopsy-based CGP, and with the TSO 500 ctDNA v2 assay we've aimed to make it easier for customers to integrate and enable deeper insights for cancer research," said Kevin Keegan, general manager of Oncology at Illumina.

Key improvements

• Total turnaround time decreased to less than four days. Library preparation has been reduced to a single day, with improved chemistry requiring a single hybridization step, driving total turnaround time down to less than four days. Most ctDNA CGP assays have a turnaround time of one week or more, but in order for biomarker results to be the most valuable, users need insights sooner to better inform precision oncology efforts.
• More analytically sensitive assay with decreased input amounts. The assay enables analysis from as little as 5 to 30 nanograms (ng) of cfDNA input. At 20 ng input, it shows more than 95% analytical sensitivity with 99.9995% specificity. At 10 ng input, it shows more than 95% sensitivity for hot-spot mutations with 99.9995% specificity. Improved performance can be attributed to both innovations in chemistry and the advanced variant analysis powered by DRAGEN.
• Flexible, streamlined, complete solution. The assay offers broader access to a sample-to-answer distributed solution in both manual and, coming in 2024, automated formats. Workflow improvements reduce hands-on time for library preparation, and automated bioinformatics features further streamline the experience. The assay provides additional flexibility with sequencing compatibility on the NovaSeq 6000 (NovaSeq 6000Dx in research mode and NovaSeq X coming in 2024), as well as local and cloud-based bioinformatics options accommodating the range of institutional preferences.

Nine institutions are participating in Illumina's global early-access customer program to trial TSO 500 ctDNA v2. Giancarlo Pruneri, professor of Pathology at the University of Milan School of Medicine and chair of the Department of Pathology and Laboratory Medicine at the National Cancer Institute of Milan, noted that preliminary testing of the new version of the TSO500 ctDNA panel in their labs "undoubtedly represented an improvement over the previous version."

"In particular, the optimization of library preparation protocol saves one working day, thus enabling a faster delivery of the molecular analysis," he said, "while the increased assay sensitivity allows the analysis of samples with reduced DNA content (20 ng), potentially broadening the utility of liquid biopsy testing."

Growing evidence on the utility and efficacy of liquid biopsy CGP is leading to its inclusion in recommended professional guidelines in oncology. Most notably, liquid biopsy testing in non-small-cell lung cancer has proven useful when tissue results are either unavailable or delayed. This trend is expected to continue for other solid tumor malignancies, which supports the consideration of broad tumor profiling from cfDNA from blood even before tissue analysis.

"Traditional tissue-based analyses are frequently still limited by tissue availability, often involving costly and invasive biopsy procedures," Pruneri said. "In this context, Illumina's new panel emerges as a solution to address the dependency on tissue availability."

Expected in the first half of 2024, automation-enabled kits and method for TSO 500 ctDNA v2 will allow laboratories to scale with the growing demand for this technology.