Solid Tumors NRAS Mutation Analysis

Test Code:

5100
Department:

Solid Tumors
Test Synonyms:

NRAS Gene Mutation (exons 1, 2)
CPT Code(s):

81404

Background:

Activating mutations in NRAS are present in approximately 20% of malignant melanomas. Based on pre-clinical data, the presence of a mutation may predict for sensitivity to RAF and/or MEK kinase inhibitors. Clinical trials for the treatment of NRAS-positive melanomas with these compounds are ongoing.

Methodology:

1. Microscopic examination of the specimen and macrodissection of tumor-rich areas.
2. DNA extraction and purification.
3. PCR amplification of NRAS coding exons 1 and 2.
4. Screening for mutations by one of two methods.

a. Real-time PCR with high resolution melting curve analysis (HRM). DNA sequencing is used to confirm any potential mutations identified by this approach.
b. Direct, bidirectional Sanger sequencing

5. Estimated sensitivity: 20% mutant allele.
6. Estimated specificity: 99.5% of NRAS mutations reported in melanoma.

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.

References:

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.
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.
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: