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Multiple Endocrine Neoplasia Type 4 via the CDKN1B Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
9205 CDKN1B 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9205CDKN1B81479 81479,81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn 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

  • Hannah Cox, PhD

Clinical Features and Genetics

Clinical Features

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder distinguished by tumors of the parathyroid glands, pancreatic islet cells, and anterior pituitary gland (Pannett and Thakker Endocrine-Related Cancer 6:449-473, 1999). Some patients with MEN1 may also develop adrenal cortical tumors, carcinoid tumors, facial angiofibromas, collagenomas, or lipomas. Neoplasia of endocrine glands typically leads to excessive hormone production. As a result, the clinical manifestations of MEN are directly related to the sites of the tumors. For example, ~95% of patients exhibit hypercalcemia, nephrolithiasis, or osteitis fibrosa cystica due to parathyroid tumors; ~40% have recurrent peptic ulcers, hypoglycemia, or hyperglucagonaemia due to pancreatic tumors; and ~30% have hyperprolactinaemia, hypercorticism (i.e. Cushing’s syndrome), or acromegaly due to anterior pituitary tumors. Approximately 30% of patients with a MEN1 phenotype test negative for variants in the MEN1 gene (Ozawa et al. J Clin Endocrinol Metab 92(5):1948-51, 2007). Multiple endocrine neoplasia was identified in a rodent model (MENX), and this helped identify variants in the human homolog CDKN1B. Patients with a MEN1-like phenotype who are positive for CDKN1B variants have been deemed to have multiple endocrine neoplasia type IV (MEN4). The clinical features of MEN4 are not clearly defined due to the limited number of patients reported. However, pituitary and parathyroid cancers as well as other malignancies have been identified (Marinoni and Pellegata. Neuroendocrinology 93:19–28, 2011).

Genetics

Heterozygous germline variants in the CDKN1B gene predispose individuals to multiple endocrine neoplasia type 4 (Pellegata et al. PNAS 103:15558-15563, 2006; Marinoni and Pellegata. Neuroendocrinology 93:19–28, 2011). CDKN1B encodes the cyclin-dependent kinase inhibitor 1B (p27, Kip1), which acts as a tumor suppressor by binding to cyclin/Cdk complexes and inhibiting cell cycle progression (Sherr & Roberts, Genes Dev 13:1501-1512, 1999). Variants to date include missense variants, a regulatory variant, a small insertion, and a small deletion (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PG-Select

Analytical sensitivity for variants in CDKN1B should be high because variants reported to date include missense variants, a regulatory variant, a small insertion, and a small deletion (Human Gene Mutation Database). This test is predicted to detect a causative variant in ~3% of MEN1 patients without a detectable variant in MEN1 (Georgitsi et al. J Clin Endocrinol Metab 92(8): 3321-5, 2007).

Clinical sensitivity for gross deletions/duplications is currently unknown.

Testing Strategy

This test provides full coverage of all coding exons of the CDKN1B gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients diagnosed with MEN1 but who test negative for a variant in the Menin (MEN1) gene. This test is specifically designed for heritable germline variants and is not appropriate for the detection of somatic variants in tumor tissue.

Gene

Official Gene Symbol OMIM ID
CDKN1B 600778
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Multiple Endocrine Neoplasia, Type IV AD 610755

Related Test

Name
Familial Isolated Pituitary Adenoma via the AIP Gene

Citations

  • Georgitsi, M., et.al. (2007). "Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia." J Clin Endocrinol Metab 92(8): 3321-5. PubMed ID: 17519308
  • Marinoni and Pellegata. (2011) "p27kip1: a new multiple endocrine neoplasia gene?" Neuroendocrinology 93:19–28. PubMed ID: 20980721
  • Ozawa et al. (2007). "The parathyroid/pituitary variant of multiple endocrine neoplasia type 1 usually has causes other than p27Kip1 mutations." J Clin Endocrinol Metab 92(5):1948-51. PubMed ID: 17299066
  • Pannett, A. A., Thakker, R. V. (1999). "Multiple endocrine neoplasia type 1." Endocr Relat Cancer 6(4): 449-73. PubMed ID: 10730900
  • Sherr, C. J., Roberts, J. M. (1999). "CDK inhibitors: positive and negative regulators of G1-phase progression." Genes Dev 13(12): 1501-12. PubMed ID: 10385618

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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 Method (Backbone)


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.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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