Test Name: ALK Kinase Domain Mutation Analysis
Synonyms: ALK, mutation, neuroblastoma, neuroblastic, anaplastic lymphoma kinase
Sample Type: ALK mutation testing can be performed on FFPE tumor specimen as well as EDTA whole blood for targeted familial ALK mutation testing.
Specimen Information: For ALK mutation testing on FFPE neuroblastic tissue: one H&E and ten 5uM unstained slides OR one H&E and two 20uM scrolls/tube x2 tubes

For targeted familial ALK mutation testing: 3cc EDTA whole blood
Specimen Transport: For ALK mutation testing on FFPE neuroblastic tissue, submit the completed Molecular Pathology Test Request form to the Pathology Molecular Oncology Lab email distribution list.

For targeted familial ALK mutation testing, submit blood specimens with completed Molecular Oncology Test Request form to Pathology Specimen Management in West Tower B.B100.
Required Information: For more information, contact Renee Webb, Manager Division of Molecular Pathology at x45032 or pager 3261. Dr. Lopez-Terrada, Medical Director, Molecular Oncology Laboratory at x41288 or pager 6409. Molecular Oncology Laboratory at x42202.
Required Forms: Requests for ALK mutation analysis on formalin-fixed paraffin-embedded (FFPE) tissue should be submitted with the Molecular Pathology Test Request form.

Requests for targeted germline analysis of the ALK gene in patients and family members should be submitted with the Molecular Oncology Test Request form.
Testing Frequency: at least weekly
Expected Turn Around Time: 5-10 business days
Clinical Application: Activating point mutations in the tyrosine kinase domain of ALK occur in 6-12% of sporadic neuroblastomas and in ~50% of familial neuroblastomas. In cooperation with NMYC, ALK mutations drive tumorigenesis and confer a worse prognosis in neuroblastoma. Crizotinib, a small molecule inhibitor of ALK currently in trials, has shown efficacy in treating cancers with ALK activation. Various ALK mutations in neuroblastomas have differential sensitivity to crizotinib. Identification of ALK mutations is an eligibility criterion for patients to receive ALK inhibitor therapy (ClinicalTrials.gov NCT00939770).

This assay targets exons 21-28 of the ALK gene that encodes the tyrosine kinase domain. Both somatic (tumor) and germline testing can be performed. Testing will initially be performed on formalin-fixed paraffin-embedded (FFPE) tissue. Detection of an ALK mutation in the tumor may lead to targeted germline analysis of the ALK gene in the patient and family members.
Test Performed By: Texas Children's Hospital Pathology Services

Available at TCH Main Campus: 832-824-5152
6621 Fannin, MC 1-2261
Houston, TX 77030-2399
Lab Section: Molecular Pathology