Neuroblastoma Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
5057 ALK 81479,81479 Order Options and Pricing
KIF1B 81479,81479
PHOX2B 81404,81403
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
5057Genes x (3)81479 81403, 81404, 81479 $930 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Neuroblastoma is the most common type of childhood cancer that occurs before 1 year of age, accounting for 10-15% of cancer deaths in children. Approximately 90% of neuroblastomas are detected by 5 years of age, while 30% are found in the first year of life with the median age of diagnosis of 22 months (Esiashvili Natia et al. 2009). This tumor type can occur in adolescence and adulthood, although the prognosis is poorer compared to a childhood incidence (Colon and Chung 2011). The majority of neuroblastomas (65%) arise in the abdomen, with half of these in the medulla of the adrenal gland. They can also occur in the chest (20%), neck (5%), pelvis (5%), and in 1% of cases have an unknown primary (Colon and Chung 2011). Symptoms of patients with neuroblastoma include malaise, fevers, weight loss, enlarging mass, pain, and abdominal distention. Other symptoms can include early-onset hypertension and tachycardia due to the secretion of catecholamines. Neuroblastomas commonly occur sporadically in a family, but 1-2% of cases occur with family histories of neuroblastoma. Hereditary neuroblastomas tend to have earlier presentations and lead to multiple primary cancers. They also show significant clinical heterogeneity, whereby a pedigree may show an individual with spontaneous cancer regression, whereas another individual with metastatic spread (Deyell and Attiyeh 2011). Siblings of an affected patient with neuroblastoma have a 10-fold increase in developing neuroblastoma (Friedman 2005). Neuroblastomas can also be found with other conditions such as Hirschsprung disease, congenital hypoventilation disorder, and neurofibromatosis type 1 (Greengard and Park 2012).

Genetics

Hereditary neuroblastoma is an autosomal dominant disorder that shows incomplete penetrance (Fisher and Tweddle 2012). Neuroblastomas show whole-chromosome gains and segmental chromosomal aberrations. The former results from hyperdiploidy and has a favorable prognosis, whereas the latter is associated with MYCN amplification and associated with worse outcomes (Colon and Chung 2011). The most frequent genetic aberration is an unbalanced chromosome 17q gain found in 70% of neuroblastomas, which has a poor prognosis (Bown et al. 1999).

In cases of hereditary neuroblastoma, the most common etiology are pathogenic variants in the anaplastic lymphoma kinase (ALK) oncogene. ALK encodes a tyrosine kinase receptor involved in cellular differentiation, proliferation, and survival. Pathogenic variants lead to constitutive activation of kinase activity. ALK pathogenic variants are rarely found in simplex cases (Mosse et al. 2008). All reported ALK causative variants have been missense, with the majority in the kinase domain (Human Gene Mutation Database).

Another cause of hereditary neuroblastomas are PHOX2B pathogenic variants, which are often associated with Hirschsprung's disease and/or congenital hypoventilation (Mosse et al. 2004). PHOX2B encodes a transcription factor that is involved in the normal sympathetic neuronal development and catecholamine synthesis. PHOX2B pathogenic variants are rarely found in sporadic neuroblastomas (van Limpt et al. 2004). The majority of causative PHOX2B variants include missense and small insertions and deletions (Human Gene Mutation Database).

Germline pathogenic variants in KIF1B in individuals with neuroblastoma and pheochromocytomas, and possibly nonneural tumors, have been reported (Schlisio et al. 2008; Yeh IT et al. 2008). The majority of KIF1B causative variants are missense changes (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

Taken together, ALK and PHOX2B germline pathogenic variants account for 90% of hereditary neuroblastoma, with the majority being in the ALK gene (Fisher and Tweddle 2012).

Clinical sensitivity for KIF1B pathogenic variants is unknown at this time since relatively few individuals with these variants have been reported.

No gross deletions or duplications have been reported for these genes for neuroblastoma. They are expected to be rare.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.

Sanger sequencing of PHOX2B exon 3 is performed to detect the expansion of the polyalanine repeat region that may be causative for neuroblastoma.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Hereditary neuroblastoma should be suspected in neonates where there is a family history of neuroblastoma, ganglioneuroma, or ganglioneuroblastoma in two or more 1st degree relatives or in bilateral neuroblastoma (Bourdeaut et al. 2012). Genetic testing for ALK pathogenic variants should also be carried out to detect subclinical disease and to indicate the likelihood of developing neuroblastoma. Germline pathogenic variants in this gene should also be tested in minors with a family history of neuroblastoma. Prenatal diagnosis for pregnancies at increased risk for ALK-related neuroblastoma susceptibility is possible; however, such testing cannot predict if neuroblastoma will develop (Greengard and Park. 2012).

Genes

Official Gene Symbol OMIM ID
ALK 105590
KIF1B 605995
PHOX2B 603851
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Neuroblastoma 1 AD 256700
Neuroblastoma 2 AD 613013
Neuroblastoma 3 AD 613014

Related Test

Name
PGxome®

Citations

  • Bourdeaut F. et al. 2012. European Journal of Human Genetics. 20: 291-7. PubMed ID: 22071890
  • Bown N. et al. 1999. The New England Journal of Medicine. 340: 1954-61. PubMed ID: 10379019
  • Colon N.C., Chung D.H. 2011. Advances in Pediatrics. 58: 297-311. PubMed ID: 21736987
  • Deyell R.J., Attiyeh E.F. 2011. Cancer Genetics. 204: 113-21. PubMed ID: 21504710
  • Esiashvili N. et al. 2009. Current Problems in Cancer. 33: 333-60. PubMed ID: 20172369
  • Fisher J.P, Tweddle D.A. 2012. Seminars in Fetal & Neonatal Medicine. 17: 207-15. PubMed ID: 22673527
  • Friedman D. L. 2005. Cancer Epidemiology Biomarkers & Prevention. 14: 1922-7. PubMed ID: 16103438
  • Greengard and Park. 2012. ALK-Related Neuroblastic Tumor Susceptibility. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301782
  • Human Gene Mutation Database (Bio-base).
  • Mosse Y.P. et al. 2004. American Journal of Human Genetics. 75: 727-30. PubMed ID: 15338462
  • MossĂ© Y.P. et al. 2008. Nature. 455: 930-5. PubMed ID: 18724359
  • Schlisio S. et al. 2008. Genes & Development. 22: 884-93. PubMed ID: 18334619
  • van Limpt V. et al. 2004. Oncogene. 23: 9280-8. PubMed ID: 15516980
  • Yeh I.T. et al. 2008. Human Genetics. 124: 279-85. PubMed ID: 18726616

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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