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The Signatera (RUO)

The Signatera (RUO)

The Signatera (RUO)

The Signatera (RUO)

Most liquid biopsy tests use a generic panel approach to cancer detection in research without knowing if mutations assayed are relevant to a particular patient.

The Signatera (RUO) ctDNA technology, however, is truly personalized. It focuses on 16 or more mutations known to be present in a patient’s tumor sample (“tumor signatures”).

This unique approach enables high sensitivity and specificity for ctDNA detection and monitoring.1

The advantages

  • Individual-specific

    Targets more individual-specific mutations (≥16) than a generic panel approach, leading to a higher probability of ctDNA detection1

    Focusing on individual-specific mutations allows deeper sequencing1

  • High sensitivity

    Detects variant allele frequencies (VAF) down to 0.01%—one mutant copy in a background of 10,000 genomic copies1

    Identified 43% more ctDNA-positive early-stage lung cancer cases than a generic lung cancer panel in a study published by Nature1

  • High specificity

    Optimized to achieve high specificity by requiring detection of at least two mutations for a ctDNA-positive call, which minimizes false positives1

  • Scalable platform

    Customizable to track additional mutations for oncology research or clinical studies

  • Research impact

    Potential to detect residual disease, measure treatment response, and monitor recurrence, as exemplified by a longitudinal clinical study featured on the cover of Nature1

The process

Note: Steps 1 and 2 are optional if the whole-exome sequencing data are already available.

Technical specifications

Signatera (RUO) employs a personalized approach to cancer detection in plasma. By analyzing whole-exome sequencing data from a tumor sample, Signatera (RUO)’s proprietary bioinformatics pipeline is able to identify mutations that are likely to be clonal. Because clonal mutations are expected to be present in all tumor cells, these targets are optimal candidates for ctDNA detection and monitoring over time.

Based on the identified mutations, Signatera (RUO) creates approximately 16 custom assays for each individual. By targeting these 16 known mutations, it has a higher probability of detecting one or more ctDNA targets in a plasma sample when compared to a generic panel approach. Signatera (RUO) also has a very low limit of detection (LOD), which enables it to find a single mutant copy in 10 mL of plasma.1 The high number of known targets per sample and the low LOD differentiate Signatera (RUO) from previous ctDNA detection tools.

A personalized versus generic panel approach

The benefit of a personalized approach is illustrated in the table below, where an early version of the Signatera (RUO) technology was compared head to head to a generic hotspot panel within the same lung cancer cohort. Our technology identified 43% more ctDNA-positive early-stage lung cancer cases.

Comparison of personalized and generic panel approaches in ctDNA detection1

Adapted from Extended Data Table 2a in Abbosh C. et al. Nature 545, 446–451. (2017)
LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; SNVs: single-nucleotide variants



The limit of detection (LOD) is an analytical measurement based on repeated serial dilutions of known concentrations and is reported out with an associated sensitivity level. The sensitivity associated with an LOD provides the confidence around the assay’s ability to detect an analyte at the concentration of the stated LOD.

For example, a 0.01% LOD with 90% sensitivity means that an assay can detect at least one of its target molecules, in a background of 10,000 other molecules, in 90% of the samples with such a concentration. An LOD of 0.01% translates to detection of a single ctDNA molecule in two tubes of whole blood (10 mL of plasma, which contains approximately 10,000 cfDNA molecules). Using an assay with a low LOD requires sufficient input material. In other words, for an assay with the ability to detect one target in 10,000 molecules, a researcher needs to provide a sample that contains at least 10,000 molecules (10 mL of plasma).

The clinical sensitivity of an assay, however, should be derived from more than just the assay’s LOD. It is also a function of how well a marker is associated with the disease and the probability of the marker being present in a given sample. The latter is beyond an assay’s LOD and is a function of a sample’s size and the number of markers it contains.

Given the heterogeneity of cancer, even large generic panels targeting dozens of genes may have coverage of (and the potential to detect) only 0-5 mutations from a given individual’s tumor.1,3 Additionally, the concentrations of mutations in the plasma are often less than 0.1%, and many mutations may not even be present in a given tube of the subject’s blood.

Signatera (RUO) was designed to track 16 or more mutations known to be present in a patient’s tumor sample, improving the probability of mutation targets being detected in a given blood sample. Combining a low LOD and a high number of known mutation targets is precisely how a personalized approach can lead to increased clinical sensitivity for ctDNA detection.1

Sample requirements

Signatera (RUO) can accept other inputs, but for optimal performance, please follow these recommendations:

Primary tissue*

One of the following:

  • Tissue block and 1 H&E slide (preferred)
  • 10 unstained slides and 1 H&E slide (10 micron thickness)
  • 4-6 cores from core needle biopsies and 1 H&E slide


One of the following:

  • Two tubes of whole blood collected in Streck® tubes or 10 mL of double-spun plasma
  • EDTA tubes are acceptable under certain conditions. Please contact us for further information.

*Optional if the whole exome sequencing data are already available

Contact us with questions.

Learn more about
Signatera (RUO)’s applications



  1. Abbosh C. et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature 545, 446–451. (2017)
  2. Data on file at Natera
  3. Hamblin A. et al. Clinical applicability and cost of a 46-gene panel for genomic analysis of solid tumours: retrospective validation and prospective audit in the UK National Health Service. PLOS Medicine 14, e1002230. (2017)
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