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Multiple Endocrine Neoplasia Type 2A (MEN2A), Type 2B (MEN2B), and Familial Medullary Thyroid Carcinoma (FMTC) via the RET 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
4673 RET 81406 81406,81479 $540 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4673RET81406 81406,81479 $540 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 2 (MEN2) is characterized by medullary thyroid carcinoma (MTC) and classified into three subtypes: MEN2A, FMTC and MEN2B (Marquard and Eng. 2015. PubMed ID: 20301434).

MEN2A is characterized by the occurrence of one or more specific endocrine tumors in a single individual or in close relatives: MTC, pheochromocytoma, or parathyroid adenoma/hyperplasia.

FMTC (familial medullary thyroid carcinoma) is diagnosed in families with more than one case of MTC in the absence of pheochromocytoma or parathyroid adenoma/hyperplasia.

MEN2B is characterized by the early development of an aggressive form of MTC, pheochromocytoma in association with a "Marfanoid" body habitus and mucosal neuromas of the lips and tongue (Morrison and Nevin. 1996. PubMed ID: 8880581).

Genetics

MEN2A/MEN2B/FMTC is inherited in an autosomal dominant manner with near complete penetrance. These disorders are caused by constitutively activating (gain-of-function) mutations of the RET proto-oncogene. The majority of families with MEN2A have a RET mutation in exon 10 or 11. Mutations of codon 634 encoding cysteine occur in about 85% of families. MEN2A comprises about 70%-80% of cases of MEN2.

Common cysteine codon mutations in exon 10 and 11 as well as other non-cysteine codon mutations in exon 8 and 13-15 have been reported in FMTC. FMTC comprises about 10%-20% of cases of MEN2. Evidence for genotype-phenotype correlation involving specific cysteine codons has been established (Eng et al. 1996. PubMed ID: 8918855; Niccoli-Sire et al. 2001. PubMed ID: 11502806).

Over 95% of MEN2B patients have the same germline mutation in the tyrosine kinase domain of RET: p.Met918Thr in exon 16 (Eng et al. 1996. PubMed ID: 8918855). Somatic mutations at this codon are frequently observed in individuals with sporadic MTC. Another mutation (p.Ala883Phe) in exon 15 has been reported in 2-4% of cases. MEN2B comprises about 5% of cases of MEN2.

The RET proto-oncogene is one of the receptor tyrosine kinases, cell-surface molecules that transduce signals for cell growth and differentiation. RET interacts with the glial-derived neurotropic factor (GDNF) family of ligands: GDNF, neurturin, persephin, and artemin. Formation of a complex containing two RET protein molecules leads to RET autophosphorylation and intracellular signaling (Santoro et al. 2004. PubMed ID: 15331579).

Clinical Sensitivity - Sequencing with CNV PG-Select

This test is predicted to detect pathogenic sequence variants in >98% of cases with MEN2A, and MEN2B, and >95% of cases with FMTC (Marquard and Eng. 2015. PubMed ID: 20301434; Mulligan et al. 1994. PubMed ID: 7907913; Mulligan and Ponder. 1995. PubMed ID: 7608246; Shirahama et al. 1998. PubMed ID: 9621513; Eng et al. 1996. PubMed ID: 8918855; Niccoli-Sire et al. 2001. PubMed ID: 11502806). To our knowledge, no pathogenic copy number variants in RET have been associated with MEN2A, MEN2B or FMTC.

Testing Strategy

This test provides full coverage of all coding exons of the RET 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 with clinical features consistent with MEN2A, MEN2B and/or FMTC.

Gene

Official Gene Symbol OMIM ID
RET 164761
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Hirschsprung Disease (HSCR) via the RET Gene
Hirschsprung Disease (Non-syndromic) Panel

Citations

  • Eng et al. 1996. PubMed ID: 8918855
  • Marquard and Eng. 2015. PubMed ID: 20301434
  • Morrison and Nevin. 1996. PubMed ID: 8880581
  • Mulligan and Ponder. 1995. PubMed ID: 7608246
  • Mulligan et al. 1994. PubMed ID: 7907913
  • Niccoli-Sire et al. 2001. PubMed ID: 11502806
  • Santoro et al. 2004. PubMed ID: 15331579
  • Shirahama et al. 1998. PubMed ID: 9621513

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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