From scientists conducting cancer research, to those developing cancer diagnostics and therapeutics, to oncologists treating cancer patients, we are all working towards a common goal of helping cancer patients live long, satisfying lives. Advances in knowledge of cancer biology and diagnostic or therapeutic innovations are at the forefront of helping to reach that goal. It is now established that cancer is a set of genetic diseases, with accumulated genetic aberrations sustaining the uncontrolled growth of malignant cells.
These aberrations include mutations, chromosomal copy number changes and gene fusions. In recent years, large-scale sequencing efforts have revealed the most common genomic aberrations across a range of tumour types. To better treat the disease, pharmaceutical companies are working to develop therapies effective in targeting these common aberrations.
The challenge is matching the right patient to the right drug. Clinical research suggests that cancer patients have better outcomes when treated with therapies matched to the genetic aberrations in their tumours than cancer patients who are treated with more generally applied therapies. Precision oncology is a term used to describe the effort to match the right patient to the right drug at the right time. Key to meeting this goal is identification of the relevant genomic aberrations present within a patient’s disease.
Clinical research suggests that cancer patients have better outcomes when treated with therapies matched to the genetic aberrations in their tumours than those who are treated with more generally applied therapies
Companies such as Thermo Fisher Scientific are working in tandem to develop tests that can help identify the genetic aberrations linked to targeted therapies. Currently, these tests are for research applications only, but are provided to support research that will lead to the development of diagnostics. To this end, Thermo Fisher Scientific provides intelligently designed next-generation sequencing (NGS) panels that allow researchers to understand published somatic aberrations, and thereby assist the development of precision oncology.
Targeted sequencing – ideal for use in cancer diagnostics: Whole genome, exome and transcriptome sequencing have proven to be invaluable approaches for researching and characterising tumours, but are not financially or logistically sustainable in meeting the needs of clinicians implementing precision oncology. By comparison, targeted sequencing approaches are capable of capturing the majority of relevant alterations and can be achieved with lower cost and shorter timelines.
By combining knowledge of the most common published somatic aberrations with the cost effectiveness and efficiency of targeted sequencing, Thermo Fisher Scientific is leading the shift from the paradigm of single gene tests to currently research focused multiplexed, multi-gene NGS tests.
Two products strategically designed to target published somatic genomic aberrations are the Oncomine Focus Assay and the Oncomine Comprehensive Assay. These offerings, combined with Ion AmpliSeq library preparation technology and Ion Torrent NGS, provide an NGS solution for research supporting the development of diagnostic applications.
Ion AmpliSeq technology: This technique transforms genetic research by delivering ultra-high multiplex PCR with low DNA input requirements. With the ability to multiplex hundreds or even thousands of PCR primer pairs in one tube, researchers are no longer limited to sequencing just a few genes, but can quickly and easily analyse hundreds of gene targets. The breakthrough minimal requirement input of 10ng DNA per reaction enables researchers to analyse highly challenging samples, like those derived from formalin-fixed, paraffin embedded (FFPE) tissues, previously not amenable to sequencing due to limited amounts of available genetic material.
Ion Torrent NGS: Ion Torrent semiconductor sequencing is a method of DNA sequencing that is based on the detection of hydrogen ions that are released during the polymerisation of DNA. It does not require any modified nucleotides or special optical detection methods, enabling faster sequencing runs and time to result.
Ion Torrent semiconductor sequencing is based on the detection of hydrogen ions that are released during the polymerisation of DNA. It does not require any modified nucleotides or special optical detection methods, enabling faster results
Detecting published somatic aberrations in solid tumours: Thermo Fisher Scientific has the capability of leveraging the knowledge captured in the world’s most comprehensive collection of cancer genomic data (the Oncomine Knowledgebase). The Oncomine Focus Assay was designed using this knowledge base for translational and clinical research laboratories. This new multi-biomarker NGS panel includes 52 solid tumour genes that are associated with current oncology drugs and published evidence (see Table 1). This assay includes genes targeting hotspots, focal copy gains and gene fusions.
| Table 1: Current oncology drugs and published evidence linked to the Oncomine Focus Assay and Oncomine Comprehensive Assay | ||
| Oncomine Focus Assay (52 genes) | Oncomine Comprehensive Assay (143 genes) | |
| Oncology drug labels | 12 | 12 |
| NCCN clinical guidelines | 9 | 9 |
| Clinical trials | >300 | >300 |
| Drug targets | 41 | 72 |
| Targeted therapies | 165 | 175 |
| Drug targets indicates the number of genes on each assay that are identified as biological targets of a drug (preclinical or clinical), while targeted therapies indicates the number of targeted therapies in clinical development associated with a gene on each assay. | ||
The Oncomine Comprehensive Assay was designed for retrospective biomarker analysis and includes 143 solid tumour genes including oncogenes, tumour suppressor genes, genes subject to focal copy gain, and gene fusions.
The ability to detect a broad range of genomic variants in one targeted sequencing panel eliminates the expensive, time-consuming process of sequential testing of tumour samples with single gene tests, which does not always yield the necessary information before the tumour sample is exhausted. Furthermore, the minimal sample requirement is applicable even to challenging samples such as FFPE tissue and retrospectively collected tumour biopsies.
The Oncomine Focus Assay at a glance
- Covers aberrations found in 52 unique genes across solid tumours
- Allows interrogation of hotspot SNVs, indels, copy number variants and gene fusions in a single run
- Minimal sample requirements (10ng DNA, 10ng RNA per run), compatible with FFPE samples
- Fast turn-around times: sample to report in three days
- Ability to multiplex at least six samples per run on the Ion Torrent Personal Genome Machine
- Currently designed for oncology research; not for use in diagnostic procedures. This assay is planned to be the building block for future development of an IVD multi-marker oncology panel.
The Oncomine Comprehensive Assay at a glance
- Covers aberrations found in 143 unique genes across solid tumours
- Allows interrogation of hotspot SNVs, indels, copy number variants, and gene fusions in a single run
- Minimal sample requirements (20ng DNA, 10ng RNA per run), compatible with FFPE samples
- Fast turn-around times: sample to report in three days
- Designed for one sample per run on the Ion Torrent Personal Genome Machine or for 12 samples per run on the Ion Proton System
- Currently designed for oncology research; not for use in diagnostic procedures
- Chosen for use in the National Cancer Institute’s Molecular Analysis for Therapy Choice (MATCH) trial
In support of these assays, a file that summarises the published evidence associated with the gene aberrations is provided. The information includes annotation of the gene aberrations specified in oncology drug labels and National Comprehensive Cancer Network (NCCN) guidelines, as well as examples of open clinical trials utilising the gene aberrations as enrollment criteria.
With resources such as these, Thermo Fisher Scientific is well positioned to contribute to precision oncology. One day, it may be possible to imagine every cancer patient having access to fast, efficient and affordable precision oncology approaches and having the best opportunity of improved outcome.
Oncomine, Ion AmpliSeq and Ion Torrent are all registered trademarks of Thermo Fisher Scientific.
The authors
Mary Ellen Urick, Mark Tomilo, David Galimberti, Kenneth Kopp, Emma Bowden and Seth Sadis, Thermo Fisher Scientific, Genetic, Medical and Applied Sciences Division
