• Test Code:
  • Department:
  • Test Synonyms:
    BRAFNRASKIT for melanoma
  • CPT Code(s):

Mutations in the BRAF gene are the most common oncogenic alterations in malignant melanoma, present in approximately 45% of tumors arising from cutaneous sites. BRAF kinase inhibitors such vemurafenib may be effective against tumors with BRAF mutations.

Mutations in the NRAS gene are the second most common oncogene alterations in malignant melanoma. There is pre-clinical evidence that tumors with these mutations may be sensitive to MEK kinase inhibitors, and clinical trials of these inhibitors are now ongoing.

Activating mutations of the KIT tyrosine kinase are present in some cases of malignant melanoma. The frequency varies with primary site, as indicated in this table.

Sites All cutaneous Sun-damaged skin Anorectal/vaginal Nasal sinus/oral cavity Acral
% KIT mutations 1-2% ~7% 15-23% ~5% 10-15%

Two phase II trials have shown good activity of imatinib for the treatment of patients with KIT-mutant melanoma. Responses to sunitinib, dasatinib, and sorafenib have also been reported in individual cases of KIT-mutant melanoma.


The specimen is examined microscopically to identify areas of tumor suitable for testing. The tumor is then macro-dissected and DNA is extracted and purified. Selected exons of the KIT and NRAS genes are amplified by PCR, and the products are screened for mutations by one of two methods: direct, bidirectional sequencing, or real-time PCR with high resolution melting curve analysis. DNA sequencing is used to confirm any mutations picked up by melting curve analysis. The estimated sensitivity of these methods is 20% mutant allele. BRAF exon 15 is screened by Sanger sequencing using an LNA-clamp oligo, which increases sensitivity to the level of 2% mutant allele.

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):

Mon – Fri

Turn Around Time:

7-10 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.


  1. Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, Cho KH, Aiba S, Bröcker EB, LeBoit PE, Pinkel D, Bastian BC. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005 Nov 17;353(20):2135-47.
  2. Devitt B, Liu W, Salemi R, Wolfe R, Kelly J, Tzen CY, Dobrovic A, McArthur G.
    Clinical outcome and pathological features associated with NRAS mutation in cutaneous melanoma. Pigment Cell Melanoma Res. 2011 Aug;24(4):666-72.
  3. Jakob JA, Bassett RL Jr, Ng CS, Curry JL, Joseph RW, Alvarado GC, Rohlfs ML, Richard J, Gershenwald JE, Kim KB, Lazar AJ, Hwu P, Davies MA. NRAS mutation status is an independent prognostic factor in metastatic melanoma. Cancer. 2012 Aug 15;118(16):4014-23.

Additional Info:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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