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Thermo Fisher Launches Liquid Biopsy Assay Based on Tag Sequencing Technology

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NEW YORK (GenomeWeb) – Thermo Fisher Scientific has launched a liquid biopsy assay for research use only that is based on technology it dubs tag sequencing. The assay was designed to run on Thermo's Ion S5 system but does not use the AmpliSeq chemistry for target amplification.

Instead, the method relies on molecular tagging plus a two-step amplification process to enable a limit of detection of 0.1 percent, Asia Chang, director of product management at Thermo Fisher, told GenomeWeb.

Researchers at the Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) in Portugal are currently conducting a retrospective validation study of the assay in 150 lung cancer patients. They plan to publish the results soon in a peer reviewed journal, after which they will launch a prospective trial of the assay, José Luis Costa, a researcher at IPATIMUP who is leading the study, told GenomeWeb.

The assay analyzes 150 hotspot SNVs and indels in 11 genes associated with lung cancer. The assay was designed to be run with the Ion Chef sample prep instrument and the S5 sequencer, for a three-day workflow from DNA extraction to results. Using the 530 chip, eight samples can be multiplexed.

In internal validation studies, Thermo Fisher has demonstrated that the assay has a mean sensitivity and specificity of 90 percent and 98 percent, respectively, for variants with allele frequencies of 0.1 percent or higher. For variants with a 0.5 percent allele frequency or higher, the assay has a mean sensitivity and specificity of 100 percent and 98 percent, respectively.

The key to being able to detect low-frequency variants is the firm's proprietary tag sequencing technology and analysis software, Chang said. Like AmpliSeq, the tag sequencing protocol relies on creating amplicons. However, molecular tags are added prior to amplification. The software then groups the molecules into families with the same tag, Chang said, which helps to ensure that the variant calls are accurate.

Chang declined to disclose further details of the tag sequencing process because the method is proprietary.

The Oncomine Lung cfDNA Assay is specifically geared toward lung cancer, but Chang said that by the end of the year, the company would also roll out assays for breast and colon cancer.

The firm does not currently have plans to take the assay through regulatory clearance, he said. The cell-free DNA assay is "not on that pathway," Chang said, because the science behind using liquid biopsies in a clinical setting is "still being written."

Thermo's liquid biopsy assay will serve a different market than liquid biopsies being offered by companies such as Guardant Health and Foundation Medicine, he said. Those companies are offering the assays as a service, while Thermo is selling an RUO kit.

The assay will also differ from one that researchers at Mt. Sinai are using in a clinical trial of triple negative breast cancer. Researchers there plan to enroll 53 patients and analyze circulating tumor DNA, circulating tumor cells, as well as germline DNA using Thermo's AmpliSeq Hotspot and Oncomine panels on the Ion Torrent PGM and S5, respectively, as well as Cynvenio's LiquidBiopsy platform for isolating the CTCs and ctDNA.

Thermo and Cynvenio have a distribution agreement for Cynvenio's LiquidBiopsy platform, which can be combined with Thermo's Ion Chef for sample prep and the Ion PGM and AmpliSeq Cancer Hotspot Panel.

Chang said that although the new assay would also be compatible with Cynvenio's LiquidBiopsy platform, it is not part of the distribution agreement. The assay is "complementary" to the system, but while that instrument isolates both CTCs and ctDNA, the new assay is designed specifically for analyzing ctDNA, he said. The standard ctDNA isolation technique for the Oncomine Lung cfDNA assay is the MagMAX cfDNA isolation kit.

Costa's group at IPATIMUP has been working with Ion Torrent sequencing technology since 2012, when the group began converting their Sanger sequencing-based genetic tests to the PGM.

For their retrospective study of the liquid biopsy assay, the researchers have been collecting blood samples over the last two years from a 150-patient lung cancer cohort. The team has multiple samples from each patient, collected at the time of diagnosis, throughout treatment, and, in some cases, at relapse.

"We want to try to see if we can implement [the Oncomine Lung cfDNA assay] in the clinic," he said. Currently, it is used solely as a research tool, so it is not influencing patient treatment or management. Thus far, he said, the assay appears to be working well. The team typically multiplexes eight samples on one run of the S5 using the 530 chip. They extract the DNA on Monday and have results by Wednesday, which he said is "pretty quick.". One advantage of the assay, he said, is that it includes the analytical portion, "which really speeds up the process of getting a result."

Costa said that the new tag sequencing chemistry also seemed to enable the team to detect low-level allelic frequencies, down to 0.14 percent. The tag sequencing chemistry enables the molecules to be counted, and helps to reduce false positives, though he said he did not know all the details of the chemistry.

Once the team finishes its retrospective and prospective validations, Costa is interested in using the assay to monitor patients while they are on therapy. "There are not many tools now to do that," he said. "That will be one of the biggest advantages." A liquid biopsy would be especially helpful for lung cancer patients, because extracting lung tumor tissue is such an invasive procedure, he added.

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