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.
Genes sequenced in this panel include:
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: Fresh formalin-fixed paraffin-embedded (FFPE) of 5-10 μm thickness from the tumour tissue.
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%).
The content on our Molecular Cancer Services page is written by Associate Professor Mirette Saad, National Director of Molecular Genetics at Australian Clinical Labs.
Assoc. Prof. Mirette Saad
MBBS (Hons), MD, MAACB, FRCPA, PhD
Associate Professor Mirette Saad is a Consultant Chemical Pathologist and the National Director of Molecular Genetics at Australian Clinical Labs. She has a Fellowship with honours in Chemical and Molecular Pathology, with Microbiology sub-speciality, from Suez Canal University, Egypt. A/P Saad received her NHMRC sponsored PhD degree in Cancer Genetics from Melbourne University and Peter MacCallum Cancer Institute. Along with her teaching and research roles, A/P Saad is a registered medical practitioner with AHPRA, a Chemical Pathology Fellow (FRCPA) at the Royal College of Pathologists of Australasia and a Member of the Australasian Association of Clinical Biochemists (MAACB). She is a Chair of the RCPA Chemical Pathology Advisory Committee, Member of the RCPA Genetic Advisory Committee, AACB and a Chair of the Precision Medicine Services at Australian Clinical Labs. At Clinical Labs, A/Prof Mirette Saad leads the Molecular Genetic testing for non-invasive prenatal testing (NIPT), antenatal screening, personalised drug therapy and cancer.