Diagnostic Test Directory

Molecular Genetics Laboratory

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Neuroblastoma (ALK and PHOX2B Sequencing Panel)



    Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA is also acceptable.

    Volume Required

    5 ml whole blood or 3 ug extracted DNA

    Minimum Required

    3 ml whole blood


    Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday within 24 hours of collection.


    Whole blood can be refrigerated until shipment.

    Unacceptable conditions

    Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.

    Specimen Handling

    Do not heat, freeze or centrifuge blood before shipment. Refrigerate sample until shipment.

Days Performed

Mon - Fri 9:00am to 4:00pm


4-6 weeks


81479, 81404

Disease Information

Clinical Features:

Neuroblastoma is a cancer of early childhood that arises from the developing autonomic nervous system and accounts for 15% of childhood cancer mortality. Neuroblastoma usually occurs sporadically but a subset of neuroblastoma cases are inherited in an autosomal dominant manner. Heritable mutations in the anaplastic lymphoma kinase (ALK) oncogene have been shown to be the main cause of familial neuroblastoma. A small subset of patients with presumed genetic predisposition to neuroblastoma also have germline mutations in the PHOX2B gene.

Molecular Genetics:

ALK maps to chromosome 2p23 and is a tyrosine kinase transmembrane receptor with homology to neutrophin receptors and the MET proto-oncogene. Germline missense mutations have been identified mostly in the tyrosine kinase domain of the ALK gene in hereditary neuroblastomas. These missense variants are predicted to be activating mutations that result in constitutive phosphorylation of the kinase domain. Somatically acquired missense mutations in the kinase domain of the ALK gene have also been identified. PHOX2B maps to chromosome 4p12 and encodes a highly conserved homeobox domain transcription factor. PHOX2B mutations have been identified in familial as well as sporadic cases of neuroblastoma. Mutations in the PHOX2B gene also cause congenital central hypoventilation syndrome (CCHS).

Test Methods:

ALK: Mutations in the kinase domain (exons 21-28) are detected by sequence analysis. PHOX2B: Mutations in the entire coding region (exons 1-3) are detected by sequence analysis.

Detection Rate:

Although data regarding the frequency of mutations is limited, missense mutations have been identified in upto 3% of patients with germline mutations and from 6-12% in patients with a somatic mutation in the tumor. These mutations have been identified mostly in the tyrosine kinase domain of the ALK gene. The detection rate is higher in families with high risk for predisposition to neuroblastoma (High risk is 3 or more affected individuals of close relation). Research studies to determine the frequency of mutations in the ALK gene are ongoing. The frequency with which PHOX2B germline mutations are identified in patients with presumed genetic disposition to neuroblastoma (familial reoccurrence, and/or associated disorder and/or multifocal primary tumors) is ~6 -11 %.

Related Tests:

Known mutation analysis is available to family members for previously identified mutations. Prenatal Testing is available to individuals who are confirmed carriers of a mutation. Please contact the laboratory director to discuss appropriateness of testing prior to collecting a prenatal specimen.


Test results with interpretation will be mailed and/or faxed to the referring physician following completion of the test. Additional reports will be provided as requested.


The clinical utility of the assay is in assessing the risk to other first degree relatives by genotyping at risk family members for already identified mutations, and establishing the need for continued clinical surveillance of the patient for the purpose of early detection of tumors.

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