DNA Strand

MGP-4: An NGS-based test, looking at tumour derived DNA and/or RNA, to help guide targeted therapy use

Who can this help?

Patients with common solid cancers such as lung, colorectal, and skin, whose disease is locally advanced or metastatic, should ideally receive profiling with a gene panel such as this as a matter of routine. This is because so called targeted therapies* typically represent one of the potential treatment options. It can also be used more selectively, but again for targeted therapy options, in other cancer types, e.g. breast, and gastrointestinal cancers depending upon disease sub-type, stage and treatment options being considered.
 *These are treatments that target a specific molecular aberration, often ones associated with a ‘gain of function’ effect in pathways involved in cell growth. In this context, it does not specifically include markers to help guide the use of therapies that exploit potentially aberrant repair processes, such as miss-match repair (for immune checkpoint inhibitors) or homologous repair deficiency (for PARP inhibitors) etc.

What does it do?

Analyses tumour DNA for mutations in more than 30 genes, and/or tumour RNA for 100’s of different potential gene rearrangements, to help guide what targeted therapies may be right for the patient. May also give additional information of diagnostic or prognostic use as well as identifying potential off-label treatments and/or clinical trial options. Please note that the analysis of RNA permits the detection of larger scale gene rearrangements, often referred to a gene ‘fusions’.

Why should I choose it?

This test is designed to assess the majority of genetic changes that are currently considered potentially actionable with available targeted therapies. It is frequently requested both for routine use and in patients considering clinical trial and off-label options, especially in cases where ‘standard of care’ testing has failed to identify which genes are driving the tumour.
The test is also highly sensitive and robust, and thus is able to cope well with small and/or compromised samples that may often be rejected by or fail with other service providers. Finally, the two components (DNA/RNA) may be requested separately, making it a highly cost effective solution if only one component required or alternatively the second component is requested on reflex (e.g. RNA-based analysis is only performed if DNA-based analysis was uninformative).

Which genes are covered?

MGP-4 DNA (SNVs & Small Indels): AKT1, ALK, BRAF, CDKN2A, CTNNB1, CXCR4, EGFR, ERBB2, ERS1, FBXW7, FGFR1, FGFR2, FGFR3, GNA11, GNAQ, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MET, MYD88, NRAS, PDGFRA, PIK3CA, POLE, PTEN, RET, SMAD4, STK11, TP53

MGP-4 DNA (Copy Number Gains – ‘CNGs’): EGFR, ERBB2, KIT, KRAS, MET, PIK3CA

MGP-4 RNA (Gene Fusions): ABL1, AKT3, ALK*, AXL, BRAF, EGFR, ERBB2, ERG, ETV1, ETV4, ETV5, FGFR1, FGFR2, FGFR3, MET, NTRK1*, NTRK2, NTRK3*, PDGFRA, PPARG, RAF1, RET*, ROS1*

*Validated for clinical use, all other gene fusions are for research use only (RUO). Also note that for reasons of clarity, fusion partners are not shown above, please click here to see the full list.

Fragmented DNA

MGP-5: An NGS-based test, looking at tumour derived DNA, to help guide PARP inhibitor use

Who can this help?

Patients with certain Homologous Repair Deficiency (HRD) associated cancers such as prostate, breast, ovarian and pancreatic, whose disease is locally advanced or metastatic may benefit from profiling with a gene panel such as this. This is because a group of drugs known as PARP inhibitors may represent one of the potential treatment options. The panel provides little or no useful information for guiding targeted therapy use, and therefore should not be used routinely in non-HRD associated cancer types and/or those where approved targeted therapies represent potential viable early treatment options.

What does it do?

Analyses tumour DNA for potential ‘loss of function’ mutations with 15 genes (full coding regions)  involved within the homologous recombination repair pathway.

Why should I choose it?

This test is designed to assess the full coding regions of all the key HRR genes upon which the use of PARP inhibitors may be indicated. Please note however that licensing indications currently vary considerably between tumour types and geographical regions (due to differences in regulatory approvals and professional guidelines). Furthermore, this assay does not provide any overall measure of genomic instability (i.e. a Genomic Instability Score or GIS), which currently a potential indication for PARPi use in ovarian cancer. If a GIS is required, we can facilitate specimen referrals on to our carefully selected partner organisations.

Which genes are covered?

MGP-5: ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCD2, MRE11, NBN, PALB2, PPP2R2A, TP53, RAD51B, RAD54L

Realtime PCR Curves

Rapid-turnaround tests, looking at selected biomarkers only to help guide key personalised therapy options

Who can these help?

Patients with common solid cancers such as lung, colorectal and skin.

What do they do?

Examines a single, or small number of genes, at a limited number of sites that have been specifically associated with response or resistance to a specific type of approved therapy in certain cancer types. Occasionally, such tests may also be performed to help refine a diagnosis and/or give prognostic information.

Why should I choose one?

As long as the sample is suitable for direct use, results will be delivered within a maximum of 2 working days. So they’re useful when time is critical and you just can’t wait for our more comprehensive NGS based tests. Please note however, that if these assays prove to be uninformative, we would always recommend reflex to a more comprehensive (e.g. NGS-based) option. This is to ensure that any of the much less common (but potentially still actionable) genetic changes, which fall outside of the scope of these rapid format assays, are not missed.

Which genetic changes are covered?

BRAF: Common variants at codon 600

KRAS: Common variants at codons 12, 13, 59, 61, 117, 146

NRAS: Common variants at codons 12, 13, 59, 61, 117

EGFR: Common variants at codons 719, 768, 790, 858, 861 & Common exon 19 deletions/exon 20 insertions

LUNG FUSIONS: Common intergenic gene rearrangements (fusions) involving ALK/ROS1/RET, plus intragenic gene rearrangement (exon 14 skipping) in MET.

MICRO-SATELLITE INSTABILITY (MSI):  Looks for instability in 7 repetitive DNA sequences, as a marker of mismatch repair deficiency, which is a potential indication for immune Check Point Inhibitor (CPI) therapy in patients with advanced solid tumours.

Full details of exactly what is encompassed by our gene panel (and retired legacy panels), including downloadable lists of all the variants evaluated, can be found on our NGS Assay Details page.

Other tests currently available for clinical use:

1) MSI & MLH-1 promoter methylation analysis

Both these tests, which were designed for use in accordance with the latest NICE and ACGS guidelines relating to Lynch Syndrome pre-screening, are available upon demand. The MSI assay is also suitable for use in identifying patients with advanced solid tumours who may benefit from immune Check Point Inhibitor (CPI) therapy.

2) Endopredict test (Myriad Genetics)

This test, produced by Myriad Genetics, but performed in-house at Sarah Cannon, is designed to assess the 10 year risk of distant breast cancer recurrence, and thus permit an evaluation of the relative risks/benefits of utilising chemotherapy after surgery to remove the primary tumour.

What’s in development?

1) Improved partner agnostic gene fusion detection

More recently targetable fusions such as the NTRKs and specifically the FGFRs have now been shown to have a much more diverse range of fusions partners that the more familiar ALK, ROS1 and RET. We are working to ensure that we can reliably detect as many of these (ideally all, via a partner agnostic solution) as possible.