Background:
ALK gene fusions are important oncogenic drivers in a number of cancer types, including non-small cell lung cancer, anaplastic large cell lymphoma, inflammatory myofibroblastic tumor, and renal medullary carcinoma. The use of ALK kinase inhibitors to treat these cancers is associated with the development of resistance due to selection of new mutations in the kinase domain that interfere with drug activity.
Sequencing the ALK kinase domain can be used to identify mutations associated with drug resistance. In addition, this sequencing can identify primary activating mutations of ALK that occur in some cases of neuroblastoma.
Recommended Use:
This test is used to identify primary ALK gene mutations in neuroblastoma and secondary drug resistance mutations in ALK gene fusions that occur after treatment with an ALK inhibitor.
Methodology:
ALK sequencing is performed on DNA from formalin-fixed, paraffin-embedded (FFPE) tumor tissue by bidirectional Sanger sequencing of the kinase domain.
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 shipping label provided.
- Contact Client Services for shipping materials and procedures at (855)535-1522
References:
- Huang D, Kim DW, Kotsakis A, Deng S, Lira P, Ho SN, Lee NV, Vizcarra P, Cao JQ, Christensen JG, Kim TM, Sun JM, Ahn JS, Ahn MJ, Park K, Mao M. Multiplexed deep sequencing analysis of ALK kinase domain identifies resistance mutations in relapsed patients following crizotinib treatment. Genomics. 2013 Feb 20. doi:pii: S0888-7543(13)00034-7.
- Ceccon M, Mologni L, Bisson W, Scapozza L, Gambacorti-Passerini C. Crizotinib-resistant NPM-ALK mutants confer differential sensitivity to unrelated Alk inhibitors. Mol Cancer Res. 2013 Feb;11(2):122-32.
Additional Info: