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Overview
Genomic profiling in precision oncology is transforming patient care, but long waiting periods for biomarker results can delay treatment decisions. The Ion Torrent Oncomine Dx Express Test, a CE-IVD solution, enables laboratories to deliver clinically relevant genomic profiles in as little as 24 hours, to aid clinicians in making timely therapy decisions.
This automated, true end-to-end solution*—from a single supplier and requiring only 20 minutes of hands-on time—can be implemented in a broad spectrum of clinical labs, even without next-generation sequencing (NGS) expertise. Ion Torrent Oncomine Reporter Dx reporting software provides biomarker results matched to approved therapies, guidelines, clinical trials, and peer-reviewed literature to aid clinicians in therapy management of cancer patients.
The Oncomine Dx Express Test enables:
Guideline recommendations
Content covers gene targets recommended by professional guidelines for multiple solid tumors, including subsitutions, insertions and deletions (indels), copy number variants, gene fusions, and splicing variants across 46 genes such as ALK, BRAF, EGFR, ERBB2, KRAS, MET, NTRK1/2/3 ROS1 and RET, among others.
Efficient use of samples
Requiring only 10 ng of DNA and RNA extracted from as little as two 5-micron FFPE slides, results can be generated from limited tissue and small biopsies. Plasma from liquid biopsy provides an additional sample type.
Fast results
Results can be generated in as little as 24 hours, enabling the integration of molecular and IHC results into one complete report to aid clinicians in making timely therapy decisions.
The Oncomine Dx Express Test covers gene targets recommended by professional guidelines. The test detects deletions, insertions, substitutions, and copy number variants from DNA and gene fusions and splicing variants from RNA across 46 genes.
The Oncomine Dx Express Test reports the following genes by alteration type from DNA and RNA extracted from formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples:
DNA | ||||
Substitutions, insertions and deletions |
| Copy number alterations | ||
| AKT1 AKT2 AKT3 ALK AR ARAF BRAF CDK4 CHEK2 CTNNB1 EGFR ERBB2 ERBB3 ERBB4 | ESR1 FGFR1 FGFR2 FGFR3 FGFR4 FLT3 GNAS HRAS IDH1 IDH2 KEAP1 KIT KRAS MAP2K1 | MAP2K2 MET NRAS NTRK1 NTRK2 NTRK3 PDGFRA PIK3CA PTEN RAF1 RET ROS1 STK11 TP53 |
| AR EGFR ERBB2 ERBB3 FGFR1 FGFR2 FGFR3 KRAS MET PIK3CA |
RNA | |
Fusions and splicing variants | |
| ALK AR BRAF ESR1 FGFR1 FGFR2 FGFR3 MET NRG1 | NTRK1 NTRK2 NTRK2 NUTM1 RET ROS1 RSPO2 RSPO3 |
Table 1: Oncomine Dx Express Test FFPE gene list
The Oncomine Dx Express Test reports the following genes by alteration type from cell free total nucleic acid (cfTNA) extracted from plasma samples:
Substitutions, insertions, and deletions | Fusion and splice variants | ||||
|---|---|---|---|---|---|
DNA | RNA | ||||
| AKT1 AKT2 AKT3 ALK AR ARAF BRAF CDK4 CHEK2 CTNNB1 EGFR ERBB2 ERBB3 ERBB4 | ESR1 FGFR1 FGFR2 FGFR3 FGFR4 FLT3 GNAS HRAS IDH1 IDH2 KEAP1 KIT KRAS MAP2K1 | MAP2K2 MET NRAS NTRK1 NTRK2 NTRK3 PDGFRA PIK3CA PTEN RAF1 RET ROS1 STK11 TP53 | ALK MET RET ROS1 NTRK1 NTRK2 NTRK3 | ||
Table 2: Oncomine Dx Express Test plasma gene list
The Ion Torrent Genexus Dx System automates the NGS workflow from patient sample to report. With automated library preparation, sequencing, and analysis involving 20-minutes of hands-on time, the Oncomine Dx Express Test on the Genexus Dx System helps reduce laboratory staff burden and the potential for human error. One intuitive IVD software facilitates tracking sample information through the workflow. On-instrument analysis and local reporting alleviate the need for specialized bioinformatics expertise.
Figure 1. Oncomine Dx Express Test workflow.
* The content provided herein may relate to products or workflows that have not been officially released or fully validated and is subject to change without notice.
The Genexus Dx System consists of the Genexus Dx Purification System, the Genexus Dx Integrated Sequencer, and Genexus Dx Software.
The Genexus Dx System features:
- Automated workflow that can be implemented in a variety of clinical lab settings
- Onboard vision system that verifies consumable placement in real-time, ensuring proper setup and reducing the potential for human errors
- Four-lane chip design that maximizes flexibility to accommodate various sample batch sizes
For more information on the Ion Torrent Genexus Dx System, please visit thermofisher.com/genexusDx
Figure 2. The Genexus Dx System.
Oncomine Reporter Dx is reporting software that matches genomic variant information with relevant therapies, guidelines, clinical trials, and peer-reviewed literature. It is an intuitive software that helps labs customize a clear and concise biomarker report, without requiring specialized oncology bioinformatics expertise.
For more information on Oncomine Reporter Dx reporting software, please visit oncomine.com/oncomine-report-dx
Performance
Extensive performance studies were conducted to establish performance characteristics of the Oncomine Dx Express Test for FFPE and plasma. For complete studies and results, see the Oncomine Dx Express Test User Guide.
Analytical accuracy study
The analytical accuracy was evaluated with 151 clinical FFPE samples from six cancer types (breast, colorectal, glioma, melanoma, non-small cell lung, and thyroid cancer) using the Oncomine Dx Express Test and two NGS-based orthogonal reference assays. The concordance evaluation study was performed at two sites.
The positive percent agreement (PPA) and negative percent agreement (NPA) were defined as the proportion of variant-positive and variant-negative specimens, respectively, as determined by the reference methods that were also determined by the Oncomine Dx Express Test.
Analytical accuracy results are summarized in the following table:
| Variant type | Reference assay | Percent agreement (%) | 95% confidence interval |
PPA | SNVs and indels | 1 | 93.44% (57/61) | (84.05%, 98.18%) |
NPA | XSNVs and indels | 1 | 99.99% (43,026/43,029) | (99.98%, 100.00%) |
PPA | CNVs | 2 | 100.00% (27/27) | (87.23%, 100.00%) |
NPA | CNVs | 2 | 99.30% (283/285) | (97.49%, 99.91%) |
PPA | Fusions | 1 | 91.67% (11/12) | (61.52%, 99.79%) |
NPA | Fusions | 1 | 99.98% (11,642/11,644) | (99.94%, 100.00%) |
Table 3. Oncomine Dx Express Test FFPE concordance
Limit of Blank study
The limit of blank was established by profiling 30 clinical FFPE samples confirmed to be variant-negative by a reference method. The study included: 2 replicates per sample, 2 reagent lots, and 11 tissue types (bladder, brain, breast, bile duct, colon, endometrium, lung, pancreas, prostate, skin, and thyroid).
For all 30 samples, the false-positive rate of the test was determined to be 0.75% for SNVs, 0% for indels, 0% for CNVs, and 0% for fusions. By definition of the Clinical and Laboratory Standards Institute (CLSI) EP17-A2, the limit of blank is zero.
Limit of Detection (LoD) study
The LoD was evaluated with 20 representative SNVs, indels, CNVs, and RNA fusions detected by the Oncomine Dx Express Test in clinical FFPE samples. The LoD is defined as the lowest variant level that can be detected at least 95% of the time.
Clinical specimens representing six cancer types (breast cancer, colorectal cancer, glioma, NSCLC, melanoma, and thyroid cancer) were used as the source of DNA and RNA. Variant-containing specimens were blended with wild-type samples, and the study included: 6 titration levels, 2 reagent lots, and 10 replicates per sample blend.
Based on a representative approach, the LoDs ranged from:
- 3.07% to 6.48% allelic frequencies for SNVs and indels (mean = 4.29% allelic frequency)
- 4.91 to 5.32 copies for CNVs
- 5.27 to 12.35 molecular counts (median = 8.85 molecular counts) and 7.87 to 207.5 reads for fusions
Precision study
The repeatability and reproducibility were evaluated using 20 representative DNA variants and RNA fusions in FFPE samples from six cancer types: breast cancer, colorectal cancer, glioma, melanoma, NSCLC, and thyroid cancer.
Three sites, with two operators and instruments per site, were used for the study. DNA and RNA was extracted from clinical FFPE samples, then blended with wild-type DNA or RNA into seven DNA blends and seven RNA blends. Two levels per blend were generated and distributed to sites and operators for testing.
The mean call rates excluding no-calls were 99.23%, 100%, and 99.69% for variant-positive SNVs/indels, CNVs, and fusions, respectively. The mean call rates excluding no-calls was 100% for wild-type DNA (negative-calls) and wild-type RNA.
Analytical accuracy study
The analytical accuracy of the Oncomine Dx Express Test for plasma was evaluated with 80 plasma samples from NSCLC comprising 40 variant-positive and 40 variant-negative samples (Table 4). The concordance study was performed at two sites that received an identical set of samples. One site used the Oncomine Dx Express Test, and the second site used an NGS-based reference assay.
The PPA and NPA were defined as the proportion of variant-positive and variant-negative specimens, respectively, as determined by the reference method and the Oncomine Dx Express Test analytical accuracy results are summarized in the following table:
| Variant type | Percent agreement % | 95% confidence interval |
PPA | SNVs and fusions | 100.00% (51/51) | (93.02%, 100.00%) |
NPA | SNVs and fusions | 99.98% (56,272/56,282) | (99.97%, 100.00%) |
Table 4. Oncomine Dx Express Test plasma concordance
Limit of Blank study
The limit of blank was established by profiling cfTNA extracted from 30 blood plasma samples from healthy donors confirmed to be variant-negative by a reference method. The study included two replicates per sample and two reagent lots.
For all 30 samples, the false positive rate was determined to be 0.20% for SNVs, 0% for indels, and 0% for fusions. By definition of CLSI EP17-A2, the limit of blank is zero.
Limit of Detection (LoD) study
The LoD was evaluated with 11 representative SNVs, indels, CNVs, and RNA fusions detected by the Oncomine Dx Express Test in clinical plasma samples. The LoD is defined as the lowest variant level that can be detected at least 95% of the time. The study included 6 titration levels, 2 reagent lots, 10 replicates per sample blend, and 2 cfTNA input levels (5 ng and 30 ng).
Based on a representative variant approach, the LoDs for SNVs and indels range from 0.65% to 1.82% allelic frequency (mean = 1.9% allelic frequency) for the 5 ng input level. The LoDs for SNVs and indels at the 30 ng input level ranged from 0.31% to 0.42% allelic frequency (mean = 0.36% allelic frequency).
The LoDs for RNA fusions at the 5 ng input level ranged from 9.9 to 19.6 molecular counts (median = 14.3 molecular counts). The LoDs for RNA fusions at the 30 ng input level ranged from 6.4 to 8.0 molecular counts (median = 7.5 molecular counts).
Precision study
The repeatability and reproducibility were evaluated using contrived cfTNA plasma samples prepared by blending cfTNA extracted from variant-positive cell lines and cfTNA from healthy donor plasma.
Three sites, with two operators and instruments per site, were used for the study. Site 1 had four instruments, and sites 2 and 3 had two instruments each. The mean call rates excluding no-calls were 99.86%, and 99.25% for variant-positive SNVs/indels and fusions, respectively.
The mean call rates excluding no-calls was 100% for wild-type DNA (negative-calls) and wild-type RNA.
For In Vitro Diagnostic Use. CE-IVD according to IVDD.
Not available in all countries including the United States. The content provided therein may relate to products that have not be officially released and is subject to change without notice.
Abbreviated Intended Use: The Oncomine Dx Express Test is a qualitative in vitro diagnostic test that uses targeted next-generation sequencing (NGS) technology, the Ion Torrent Genexus Dx System to detect deletions, insertions, substitutions and copy number gain present in 42 genes and fusions in 18 genes from DNA and RNA extracted from formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples. Oncomine Dx Express Test also detects deletions, insertions, substitutions in 42 genes and fusions in 7 genes from cfTNA extracted from plasma samples. The Oncomine Dx Express Test is intended to provide clinically relevant tumor mutation profiling information to be used by qualified health care professionals in accordance with professional guidelines as an aid in therapy management of cancer patients with solid malignant neoplasms using FFPE samples and as an aid in therapy management of cancer patients with non-small cell lung cancer using plasma samples. It is not conclusive or prescriptive for labeled use of any specific therapeutic product.
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