Personalised medicine

As personalised medicine becomes more established in clinical practice the need for cost effective, rapid turnaround genotype testing increases. The ability to test a patient for the presence of a specific mutation or biomarker at diagnosis can ensure they receive the most effective therapy based on their biological characteristics as quickly as possible.

For further details on the impact of personalised medicine please see:

Williamson and Robinson, Gene Genie, European Pharmaceutical Review 2012:
http://www.samedanltd.com/magazine/12/issue/169/article/3220

Sample Type:

• FFPE material with a minimum tumour content of 30%. Samples can be received as either the fixed block or 5 x 10 µm curls
• Cytology samples: FFPE cell blocks, as above, fixed cell pellet and other fluids and slide mounted material
• For cKIT analysis: 4.5ml EDTA blood or bone marrow in EDTA

Genotyping: Agena MassARRAY MALDI-TOF platform

Reporting times: 5 – 10 days

RAS testing in metastatic colorectal cancer

Erbitux is used as part of the first line therapy for patients with metastatic colorectal cancer and where the tumour has a wild type RAS gene sequence, defined as showing no mutation in exons 2, 3 and 4 of the KRAS and NRAS genes.

Mutation of the KRAS gene leads to constitutive activation of the KRAS protein, preventing the inhibitory effect of Erbitux. Identification of activating mutations at six codons in KRAS (codons 12,13, 59, 61, 117 and 146) is recognised to predict resistance to treatment.

Recent data presented at ECCO-ESMO-ESTRO (September 2013) revealed an increase in median overall survival in metastatic colorectal cancer patients with RAS wild type tumours receiving first line Erbitux plus FOLFIRI compared to other regimes.

In addition, there are reports that the BRAF gene mutation, V600E (c.1799T>A) also confers resistance.

Features of the NewGene RAS test:

• Assay includes 23 KRAS, 23 NRAS and 1 BRAF mutation
• Funding for this test can be accessed via NHS England or the Cancer Drugs Fund (CDF)
• > 90% samples reported within 5 day turnaround time

Referral form download

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EGFR mutation testing in non-small cell lung cancer

Gefitinib and Erlotinib are cancer therapies that inhibit the EGFR protein, disrupting the EGFR signalling pathway. As a result they are only effective in those patients whose cancer is caused by EGFR activating mutations. In addition, mutations in the downstream KRAS gene have also been shown to be biomarkers of response to therapy. The NewGene EGFR assay covers all of the mutations related to drug sensitivity.

Features of NewGene EGFR mutation test:

• Assay includes 7 point mutations in EGFR
• Mutations in codons 12 and 13 of the KRAS gene
• Deletions involving exon 19 and insertions in exon 20 in EGFR are also investigated
• > 90% samples reported within 5 day turnaround time

Referral form download

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BRAF and NRAS testing in melanoma

The drug Vemurafenib has been approved for treatment of patients with malignant melanoma with a V600E (c.1799T>A) mutation in the BRAF gene.

This mutation can be detected in the NewGene BRAF test. In addition the clinical importance of mutations in the NRAS gene is being established.

Features of the NewGene BRAF mutation analysis test

• Mutation analysis at codon 600 in BRAF including V600E
• Mutation screening at codon 13, 12, 59 and 61 of the NRAS gene

Referral form download

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Gastro-Intestinal Stromal Tumours

Gastrointestinal stromal tumours (GIST) affect the connective and supportive tissues of the digestive tract or nearby structures within the abdomen. They are a rare cancer accounting for approximately 2% of tumours in the gastrointestinal region and are highly resistant to chemotherapy. In many cases the cause is found to be activating mutations in the cKIT and PDGFRA genes and clinical evidence demonstrates that the mutation status can predict the patient response to tyrosine kinase inhibitors such as Imatinib.

Therefore the identification of the genotype of the tumour can be used to confirm diagnosis, determine the appropriate treatment response and provide prognostic information.

Features of the NewGene GIST mutation analysis test

Two step screen targeting the most frequently mutated parts of the cKIT and PDGFRA genes:

• Step 1: exon 9 and exon 11 of cKIT and exon 18 of PDGFRA
• Step 2: exons 8, 13 and 17 of cKIT and exons 12 and 14 of PDGFRA.

Together these mutations account for 80-95% of all known mutations in GIST.

Please note - step 2 analysis will only be carried out in those cases where no mutation is found during the step 1 screen.

Referral form download

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