Melanoma Molecular Biomarkers
About 44–70% of melanoma cases harbour a BRAF mutation. In cutaneous melanoma, the BRAF gene is mutated in ~60% of cases and p.V600E (c.1799T>A) accounts for more than 90% of BRAF mutations. This leads to constitutive activation of the MAPK pathway and increased cell proliferation, metastasis, and survival mechanisms. BRAF is also an important prognostic and treatment decision genetic biomarker in other cancer types 1.
The current standard for determining eligibility of patients with metastatic melanoma for BRAF-targeted therapy is tissue-based testing of BRAF mutations. Targeted therapy with anti-BRAF inhibitors (BRAFi) remains the first-line treatment for melanoma tumours that harbour a BRAF mutation, particularly in Australia 2.
Other oncogenic driver mutations have been identified in melanomas for which targeted therapies have demonstrated clinical activity. Detection of cKIT mutations may guide the selection of KIT TKIs (imatinib and sunitinib) for the melanoma treatment 3. It has been shown that melanoma patients with cKIT mutations treated with imatinib may have a better outcome compared to BRAF melanoma patients treated with BRAF inhibitors 4.
Another important oncogene, neuroblastoma RAS (NRAS) oncogene mutations have been more frequently detected in melanoma (13–25%) and in thyroid cancers (~6%) where they have been suggested to increase sensitivity to the mitogen-activated protein kinase signalling inhibitor (MEKi) 5.
1. Brose MS et al., (2002) Cancer Res 62(23):6997–7000.
2. Spagnolo F et al., (2015) Onco Targets Ther 8:157–168.
3. Minor DR et al., (2012) Clin Cancer Res 18:1457–1463.
4. Daniels M et al., (2011) Cancer Lett 312:43–54.
5. Fedorenko IV et al., (2017) Oncogene. 32:3009–3018.
Somatic Mutation | Solid Tissue Molecular Profiling in Melanoma
Melanoma Solid Tissue Gene Panel
The melanoma gene panel can detect actionable DNA alterations that guide treatment decisions as detailed below.
Gene panel includes:
How to Order: Fill out our Somatic Mutation testing request form and tick the Somatic Mutation test panel required.
Turnaround Time: 5–7 business days from the sample receipt date.
Specimen Required: Formalin-fixed paraffin-embedded (FFPE) tissue of a solid melanoma tumour.
Test Cost: Medicare rebate available if criteria is met. If criteria is not met there is an out-of-pocket fee of $230.
A negative result does not rule out the presence of a mutation that may be present but below the limits of detection for this assay (<5%).
"Rapid" (48-hr) BRAF Mutation Analysis
Used to detect BRAF mutation in the solid tumour samples from a patient, within a 48-hour turnaround from sample receipt.
Melanoma ctDNA Gene Panel
"Rapid" (48-hr) ctDNA BRAF Mutation Analysis
Used to detect a single gene target, BRAF, of circulating tumour DNA (ctDNA) in a patient’s blood, within a 48-hour turnaround from sample receipt.
The content on our Molecular Cancer Services page is written by National Clinical Director of Molecular Genetic Pathology at Australian Clinical Labs, Associate Professor Mirette Saad.
Assoc. Prof. Mirette Saad
MBBS (Hons), MD, MAACB, FRCPA, PhD
Associate Professor Mirette Saad is a Consultant Chemical Pathologist and the National Clinical Director of Molecular Genetic Pathology at Australian Clinical Labs. Associate Professor Saad obtained her fellowship in Chemical and Molecular Pathology with a clinical Microbiology sub-specialty in Egypt.
After several posts, she worked as a Medical Laboratory Director in private labs and as an Associate Professor and Examiner of Clinical Chemistry for postgraduate and undergraduate medical and nursing students at various institutions. Upon receiving the National Health and Medical Research (NHMRC) Scholarship in 2006, Associate Professor Saad commenced her PhD studies at Melbourne University and Peter MacCallum Cancer Institute in Cancer Genetics. Associate Professor Saad undertook her specialty training at Healthscope Pathology (now Australian Clinical Labs) and Monash Health and obtained the Chemical Pathology Fellowship (FRCPA) and the Membership (MAACB) by examination from the Royal College of Pathologists of Australasia (RCPA) and the Australasian Association of Clinical Biochemists (AACB) respectively.
She is currently a member of the Chemical Pathology Advisory Committee at RCPA. At Clinical Labs, A/P Saad supervises the antenatal screening program including combined First Trimester Screening and Non-Invasive Prenatal Testing (NIPT) along with the Molecular Genetic testing for hereditary disorders, personalised drug therapy and cancer.