Test Catalog

Test ID: MELP    
Melanoma Targeted Gene Panel by Next-Generation Sequencing, Tumor

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnosis and management of patients with melanoma

 

Simultaneously interrogating multiple gene targets including BRAF (eg, V600E and V600K), GNAQ, GNA11, KIT and NRAS

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test uses targeted next-generation sequencing to evaluate for somatic mutations within the BRAF (exons 11 and 15), GNAQ (exon 5), GNA11 (exon 5), KIT (exon 2, 9, 10, 11, 13, 14, 15, 17, 18), and NRAS (exons 2, 3, 4) genes. This includes, but is not limited to, the testing of somatic mutations in NRAS codons 12, 13, 61,146; GNA11 and GNAQ codon 209; and BRAF codons 594, 596, 600 (e.g. V600E/K). See Targeted Gene Regions Interrogated by Melanoma Panel in Special Instructions for details regarding the targeted gene regions identified by this test.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, slide review will always be performed at an additional charge.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Targeted cancer therapies are defined as antibody or small molecule drugs that block the growth and spread of cancer by interfering with specific cell molecules involved in tumor growth and progression. Multiple targeted therapies have been approved by the FDA for treatment of specific cancers. Molecular genetic profiling is often needed to identify targets amenable to targeted therapies and to minimize treatment costs and therapy-associated risks.

 

Next generation sequencing has recently emerged as an accurate, cost-effective method to identify mutations across numerous genes known to be associated with response or resistance to specific targeted therapies. MELP / Melanoma Targeted Gene Panel by Next Generation Sequencing, Tumor is a single assay that uses formalin-fixed paraffin-embedded tissue to assess for common mutations in the following genes known to be associated with melanoma: BRAF, GNA11, GNAQ, KIT, and NRAS. This includes the common BRAF V600E and V600K mutations. The results of this test can be useful for assessing prognosis and guiding treatment of individuals with melanoma.

 

See Targeted Gene Regions Interrogated by Melanoma Panel in Special Instructions for details regarding the targeted gene regions identified by this test.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretative report will be provided.

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test cannot differentiate between somatic and germline alterations. Additional testing may be necessary to clarify the significance of results if there is a potential hereditary risk. DNA variants of uncertain significance may be identified.

 

A negative (wild-type) result does not rule out the presence of a mutation that may be present but below the limits of detection of this assay (approximately 5%-10%). This test does not detect large single or multiexon deletions or duplications or genomic copy number variants.

 

Rare polymorphisms may be present that could lead to false-negative or false-positive results. Test results should be interpreted in the context of clinical findings, tumor sampling and other laboratory data. If results obtained do not match other clinical or laboratory findings, please contact the laboratory for updated interpretation. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

Reliable results are dependent on adequate specimen collection and processing. This test has been validated on formalin-fixed, paraffin-embedded tissues; other types of fixatives are discouraged. Improper treatment of tissues, such as decalcification, may cause PCR failure.

 

Mutations in these genes can be seen in neoplasms other than melanoma. For KIT Asp816Val mutation analysis in mast cell disease, refer to KITAS / KIT Asp816Val Mutation Analysis, Qualitative PCR.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Carvajal RD, Antonescu CR, Wolchok JD, et al: KIT as a therapeutic target in metastatic melanoma. JAMA 2011;305(22):2327-23342. Postow MA, Carvajal RD: Therapeutic implications of KIT in melanoma. Cancer J 2012;2:137-141

3. Johnson DB, Sosman JA: Update on the targeted therapy of melanoma. Curr Treat Options Oncol 2013;2:280-292

4. Anderson S, Bloom K, Vallera D, et al: Multisite analytic performance studies of a real-time polymerase chain reaction assay for the detection of BRAF V600E mutations in formalin-fixed paraffin-embedded tissue specimens of malignant melanoma. Arch Pathol Lab Med 2012 Nov;136(11):1385-1391

5. Chapman P, Hauschild A, Robert C, et al: BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011 Jun 30;364(26):2507-2516

6. Dhomen N, Marais R: BRAF signaling and targeted therapies in melanoma. Hematol Oncol Clin North Am 2009 Jun;23(3):529-545

7. Flaherty K, Puzanov I, Kim K, et al: Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010 Aug 26;363(9):809-819

8. Ascierto P, Schadendorf D, Berking C, et al: MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study. Lancet Oncol 2013 Mar;14(3):249-256

9. Jakob J, Bassett R, Ng C, et al: NRAS Mutation status is an independent prognostic factor in metastatic melanoma. Cancer 2012 Aug 15;118(16):4014-4023

10. Van Raamsdonk C, Griewank K, Crosby M, et al: Mutations in GNA11 in uveal melanoma. N Engl J Med 2010 Dec 2;363(23):2191-2199

11. Kusters-Vandevelde H, Klaasen A, Kusters B, et al: Activating mutations of the GNAQ gene: a frequent event in primary melanocytic neoplasms of the central nervous system. Acta Neuropathol 2010 Mar;119(3):317-323

12. Griewank K, van de Nes J, Schilling B, et al: Genetic and clinico-pathologic analysis of metastatic uveal melanoma. Mod Pathol 2014 Feb;27(2):175-183

Special Instructions Library of PDFs including pertinent information and forms related to the test