Background:
The most common oncogenic mutations associated with ocular (choroidal/uveal) melanomas occur in the genes for two related GTP-binding proteins, GNAQ and GNA11. Rarely, these genes are mutated in cutaneous melanomas. Both gene products are involved in signal transduction from transmembrane receptors through the MAP kinase pathway. Pre-clinical studies have shown that mutations in GNA11 induced spontaneously metastasizing tumors in a mouse model. And a melanoma cell line harboring a GNAQ Q209L mutation has been shown to be sensitive to a MEK inhibitor.
Recommended Use: Screening for GNAQ and GNA11 mutations may be useful in subtyping melanomas for potential targeted therapy in clinical trials.
Methodology:
Identical hotspots in both genes (Q209 and R183) are screened by bidirectional Sanger sequencing using DNA from formalin-fixed, paraffin-embedded (FFPE) tumor tissue.
Specimen Requirements:
- A paraffin block or
- 10 unstained sections of tumor (4-5 microns) (15 sections for small biopsies)
Contact Client Services for shipping materials and procedures at (855)535-1522.
A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES. Please include detailed clinical information.
Test Performed (Days):
Twice per week
Turn Around Time:
10 - 14 days
Shipment Sensitivity Requirements:
- Keep specimen cool during transit. Do not ship on dry ice.
- Please use the cold pack provided in the KDL shipping kit.
- Ship the specimen overnight express, using the FedEx priority overnight label provided.
- Contact Client Services for shipping materials and procedures at (855) 535-1522.
References:
- CD Van Raamsdonk, V Bezrookove and G Green et al., Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi, Nature 2009 457:599–602.
- Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, Obenauf AC, Wackernagel W, Green G, Bouvier N, Sozen MM, Baimukanova G, Roy R, Heguy A, Dolgalev I, Khanin R, Busam K, Speicher MR, O'Brien J, Bastian BC. Mutations in GNA11 in uveal melanoma. N Engl J Med. 2010 363(23):2191-9.
- Falchook GS Lewis KD, Infante JR, Gordon MS, Vogelzang NJ, DeMarini DJ, Sun P, Moy C, Szabo SA, Roadcap LT, Peddareddigari VG, Lebowitz PF, Le NT,Burris HA 3rd, Messersmith WA, O'Dwyer PJ, Kim KB, Flaherty K, Bendell JC, Gonzalez R, Kurzrock R, Fecher LA. Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial. Lancet Oncol. 2012 Aug;13(8):782-9.
- Carvajal et al. Phase II study of selumetinib (sel) versus temozolomide (TMZ) in gnaq/Gna11 (Gq/11) mutant (mut) uveal melanoma (UM). J Clin Oncol 31, 2013 (suppl; abstr CRA9003).
- Wu X, Li J, Zhu M, Fletcher JA, Hodi FS. Protein Kinase C Inhibitor AEB071 Targets Ocular Melanoma Harboring GNAQ Mutations via Effects on the PKC/Erk1/2 and PKC/NF-κB Pathways. Mol Cancer Ther. 2012 Sep;11(9):1905-14.
Additional Info: