Background:
Activating mutations of the KIT tyrosine kinase are present in some cases of malignant melanoma. The frequency varies with primary site, as indicated below.
Sites
|
All cutaneous
|
Sun-damaged skin
|
Anorectal & vaginal
|
Nasal sinus & oral cavity
|
Acral
|
KIT mutations
|
1-2%
|
~7%
|
15-23%
|
~5%
|
10-15%
|
In two phase II trials of imatinib mesylate for the treatment of patients with KIT-mutant melanomas, the disease control rate (stable disease, partial or complete response) ranged from 53% to 71%,1,2 and the median progression free survival was 9.0 months.2 Responses to sunitinib,3 dasatinib,4 and sorafenib5,6 have also been reported in individual cases of KIT-mutant melanoma.
Methodology:
The testing protocol involves the following steps.
- Microscopic examination of the specimen and macrodissection of tumor-rich areas.
- DNA extraction and purification.
- PCR amplification of KIT exons 11, 13 & 17.
- Screening 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 potential mutations identified by melting curve analysis.
- The estimated sensitivity of these methods is 20% 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.
References:
- Carvajal RD, Antonescu CR, Wolchok JD, Chapman PB, Roman RA, Teitcher J, Panageas KS, Busam KJ, Chmielowski B, Lutzky J, Pavlick AC, Fusco A, Cane L, Takebe N, Vemula S, Bouvier N, Bastian BC, Schwartz GK. KIT as a therapeutic target in metastatic melanoma. JAMA. 2011; 305:2327-34.
- Guo J, Si L, Kong Y, Flaherty KT, Xu X, Zhu Y, Corless CL, Li L, Li H, Sheng X, Cui C, Chi Z, Li S, Han M, Mao L, Lin X, Du N, Zhang X, Li J, Wang B, Qin S. Phase II, Open-Label, Single-Arm Trial of Imatinib Mesylate in Patients With Metastatic Melanoma Harboring c-Kit Mutation or Amplification. J Clin Oncol. 2011 29(21):2904-9
- Zhu Y, Si L, Kong Y, Chi Z, Yuan X, Cui C, Sheng X, Guo J, Shen L. Response to sunitinib in Chinese KIT-mutated metastatic mucosal melanoma. J Clin Onc Vol 27, No 15S (May 20 Supplement), 2009: e20017
- Woodman, S. E., Trent, J. C., Stemke-Hale, K., Lazar, A. J., Pricl, S., Pavan, G. M., Fermeglia, M., Gopal, Y. N., Yang, D., Podoloff, D. A., et al. Activity of dasatinib against L576P KIT mutant melanoma: molecular, cellular, and clinical correlates. Mol Cancer Ther 2009; 8:2079-2085.
- Quintas-Cardama, A., Lazar, A. J., Woodman, S. E., Kim, K., Ross, M., and Hwu, P. Complete response of stage IV anal mucosal melanoma expressing KIT Val560Asp to the multikinase inhibitor sorafenib. Nat Clin Pract Oncol 2008; 5:737-740.
- Handolias D, Hamilton AL, Salemi R, Tan A, Moodie K, Kerr L, Dobrovic A, McArthur GA. Clinical responses observed with imatinib or sorafenib in melanoma patients expressing mutations in KIT. Br J Cancer. 2010; 102(8):1219-23.
Additional Info: