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Detection of cancer driver variants and assessment of tumor mutational burden (TMB), an emerging immuno-oncology biomarker, with next-generation sequencing

Immune checkpoint inhibitors have changed the treatment paradigm for a variety of cancers, but not all patients will respond to immunotherapies. Relevant biomarkers have shown to be as important as the therapies since they guide in our quest to help match patients with the appropriate treatment.

Our multi-biomarker next-generation sequencing (NGS)-based assays have been adopted by leading cancer institutions to comprehensively profile thousands of clinical research samples (one example is the NCI-Match Trial Assay). Given the complexity of the immune response and tumor biology, additional biomarkers are needed to evaluate their associations with response to immuno-oncology (I-O) therapies.  Tumor mutational burden (TMB) is an exciting biomarker in multiple disease types that may further immunotherapy research.

The Ion Torrent Oncomine Tumor Mutation Load Assay is a robust, targeted next-generation sequencing (NGS) assay designed for tumor profiling by annotation of cancer driver variants and provides accurate quantification of TMB from limited formalin- fixed, paraffin-embedded (FFPE) samples. Our streamlined, built-in analysis solution allows you to confidently detect cancer driver variants and assess tumor mutational burden in ~2.5 days for your research studies.

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Featured webinar and video

Video: How can the tumor mutation burden be a game changing immuno-oncology biomarker
Speaker: Dr Wolfram Jochum, Institute of Pathology, Kantonsspital St.Gallen, Switzerland

The next immuno-oncology biomarker

Jose-machado
Tumor mutation load may be the next immuno-oncology biomarker to be implemented in our daily routine clinical research. We used the Oncomine Tumor Mutation Load Assay on a retrospective colon cancer cohort, and were able to separate high and low mutation load samples with results correlating well with the MSI status of the tumors. The assay yielded rapid and robust results with its streamlined informatics. Together with other Oncomine assays, we truly have a comprehensive solution for tumor samples.

Prof. José Carlos Machado, PhD
Board of Directors member and Group Coordinator
Ipatimup, Porto, Portugal


Faster TMB insights: from sample-to-answer in less than 3 days

Our streamlined solution allows you to confidently quantify somatic mutations and assess TMB with limited sample amounts.  For maximum throughput, eight samples can be multiplexed per Ion 540 Chip, in manual and automated library preparation.

workflow-Prep-seq-analyse

Prepare libraries with the Oncomine Tumor Mutation Load Assay, using as little as 20 ng of DNA FFPE input.

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Prepare templates manually or with the Ion Chef Instrument for an automated workflow.

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 Total hands-on time: 30 minutes

Sequence your samples with an Ion GeneStudio S5 Series system and Ion 540 or Ion 550 Chip.

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 Total hands-on time: < 15 minutes

Analyze your data with the Ion Reporter Software workflow for TMB in w5.10.

Test drive Ion Reporter Software ›

Prepare libraries with the Oncomine Tumor Mutation Load Assay, using as little as 20 ng of DNA FFPE input.

Buy now ›

Prepare templates manually or with the Ion Chef Instrument for an automated workflow.

Get a quote ›

 Total hands-on time: 30 minutes

Sequence your samples with an Ion GeneStudio S5 Series system and Ion 540 or Ion 550 Chip.

Get a quote ›

 Total hands-on time: < 15 minutes

Analyze your data with the Ion Reporter Software workflow for TMB in w5.10.

Test drive Ion Reporter Software ›


The Ion Reporter analysis workflow has been designed to generate results with a tumor-only workflow. Using the Oncomine Variant Annotator Plugin, driver variants are separated from passenger mutations, allowing the user to focus on the relevant few specific to targeted therapies.  A simple TMB readout (Mutations/Mb) is provided in addition to a detailed analysis of mutation signatures, providing meaningful insights for researching the disease etiology (Figure 1).

Figure 1.

A targeted NGS panel can replace exome sequencing, bringing the advantage of a robust assay designed for oncology research specimens such as FFPE tissue. The Oncomine Tumor Mutation Load Assay enables accurate measurements of somatic mutations without the need of a matched normal sample. As panels become smaller in size, the zone of uncertainty associated with estimates of TMB expands rapidly (Figure 2A). Additionally, the coefficient of variance increases rapidly when the size of targeted panels is less than 1 Mb (Figure 2B), especially at low mutation loads. The Oncomine Tumor Mutation Load Assay covers a large genomic footprint of 1.7 Mb, encompassing 1.2 Mb of exonic sequence, to enable accurate mutation counts for samples with a range of tumor mutational burden.

High reproducbility
TMB was measured by running the assay on eight pairs of replicates. The TMB values were highly correlated (Pearson’s R = 0.99) and demonstrated reproducibility across multiple cancer types and sample types, from cell line DNA to FFPE samples (Figure 3A).  The Oncomine Tumor Mutation Load Assay was tested in a series of retrospectively collected colorectal cancer samples that had been typed for microsatellite instability.  As expected, high microsatellite instability samples had significantly higher TMB values than microsatellite stable samples.