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Simplifying Detection of Cancer Gene Variants

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Due to the rate of evolution of cancer and clinical genetics research, fixed content NSG panels are unable to truly reflect the latest knowledge on genes and variants of interest. It therefore goes without saying that this limitation can lead to problems.

To help researchers overcome these issues, Oxford Gene Technology (OGT) recently released its SureSeq myPanelTM NGS Custom Cancer Panels. They tell us that these new panels will provide scientists with completely customised, pre-optimised NGS panels that are relevant to their research.

To better understand the benefits of SureSeq myPanelTM and the limitations of traditional fixed content NGS panels, we spoke to David Cook, Senior Product Manager at OGT. 

AM: What are some of the limitations of traditional fixed content NGS panels?

David Cook (DC): By their nature, fixed content gene panels are limited to analysing a specific set of genes or genomic regions. Such panels are therefore only as good as the prevailing knowledge at the time of panel design. The pace of cancer research means that new disease-associated genes and regions are continually being identified, while other previously interesting regions are being ruled out. Furthermore, researchers often have interest in specific sets of genes, which may not be available in existing commercially available NGS panels, or these panels may contain many unwanted genes — increasing both the cost of sequencing and analysis complexity.

When considering the use of gene panels, it is also important to know the type of enrichment method used to capture the desired genomic regions for sequencing. Two broad categories of enrichment assays exist: amplicon (PCR) and hybridisation. As a very general rule, hybridisation-based assays, which allow removal of duplicate reads and uniform enrichment of even challenging (e.g., GC-rich and tandem repeat) regions, offer superior performance.

AM: Can you tell us more about SureSeq myPanel™ NGS Custom Cancer Panels and the benefits they offer?

DC: Hybridisation-based SureSeq myPanel NGS Custom Cancer Panels from OGT enable researchers to select baits for their specific requirements, and modify the panel with new content, as needed. OGT’s commitment to ongoing R&D means content will regularly be updated, and should specific areas of interest not yet be available, our customers can request this to be developed and receive a completely customised panel with pre-optimised probes in a matter of weeks. The existing range of panel content has been designed with experts and from current literature to target all relevant regions including intronic and splice sites to ensure the most comprehensive insight into disease-driving mutations.

Utilising hybridisation-based enrichment, the panels also deliver unparalleled coverage completeness and uniformity, allowing the detection of low-frequency variants with confidence and without the need for top up with Sanger sequencing in regions poorly covered by other panels

AM: Which cancer types are currently covered? Which are in the pipeline?

DC: Existing panel content covers a range of common cancer types, including ovarian, breast, myeloid and acute myeloid leukaemia (AML). More content is currently in development, covering chronic lymphocytic leukaemia (CLL), lung and colorectal cancers, plus, we will create entirely custom content for any genomic region on request.

AM: What makes certain genes difficult to sequence, and how can myPanel help?

DC: The majority of NGS panels use amplicon-based enrichment, which has a number of inherent challenges, such as enrichment of repeat and GC-rich regions. Furthermore, the presence of a novel variant in an amplicon primer site can lead to strand or allelic bias, or even drop-out of that region altogether. The use of hybridisation-based baits coupled with OGT’s superior bait design strategies allow SureSeq myPanel Custom Cancer Panels to overcome these issues to deliver uniform coverage across all regions of interest. For more information on SureSeq myPanel NGS Custom Cancer Panels, visit www.ogt.com/sureseq.

David Cook was speaking to Anna MacDonald, Editor at Technology Networks.